Zapalenie przyzębia – Patofizjologia i mechanizm

Zapalenie przyzębia
Patofizjologia i mechanizm

Zapalenie przyzębia (periodontitis) to przewlekła choroba zapalna tkanek przyzębia, dotykająca około 10% dorosłej populacji globalnie, charakteryzująca się dysbiozą mikrobiomu poddziąsłowego biofilmu oraz dysregulowaną odpowiedzią immunologiczną gospodarza. Kluczowymi patogenami są bakterie z kompleksu czerwonego, zwłaszcza Porphyromonas gingivalis, który poprzez liczne czynniki wirulencji i mechanizmy unikania odpowiedzi immunologicznej (m.in. wykorzystanie białka CD47) inicjuje i podtrzymuje stan zapalny. Patogeneza obejmuje zarówno odpowiedź wrodzoną (aktywację PRRs, produkcję IL-1, TNF-α, PGE2, rekrutację neutrofili i wydzielanie MMP-8), jak i adaptacyjną (akumulację limfocytów Th17 i produkcję IL-17A regulowaną przez STAT3). Zwiększony stosunek RANKL/OPG sprzyja osteoklastogenezie i resorpcji kości, co jest potwierdzone podwyższonymi poziomami RANKL i obniżonymi OPG w płynie dziąsłowym pacjentów z zapaleniem przyzębia. Metaloproteinazy macierzy (MMP-8, MMP-9) odgrywają istotną rolę w degradacji kolagenu typu I, a ich hamowanie (np. doksycykliną) może wspomagać leczenie.

Patogeneza zapalenia przyzębia

Mikrobna dysbioza jako czynnik inicjujący
Odpowiedź immunologiczna i zapalna gospodarza
Mechanizmy destrukcji tkanek
Rola metaloproteinaz macierzy (MMPs)
Mechanizmy epigenetyczne w patogenezie zapalenia przyzębia
Modele patogenezy zapalenia przyzębia
Rola czynników genetycznych w patogenezie
Zapalenie przyzębia a choroby ogólnoustrojowe

Pętla samopodtrzymująca w zapaleniu przyzębia
Potencjalne strategie terapeutyczne
Znaczenie patogenezy zapalenia przyzębia

Kolejne rozdziały

Patogeneza zapalenia przyzębia

Zapalenie przyzębia (periodontitis) to powszechna choroba zapalna jamy ustnej dotykająca około 10% globalnej populacji dorosłych, ze zwiększoną podatnością związaną z wiekiem¹. Choroba charakteryzuje się przewlekłym stanem zapalnym tkanek otaczających ząb, prowadzącym do stopniowej destrukcji aparatu podporowego zęba i ostatecznie do jego utraty²³. Współczesne poglądy na patogenezę zapalenia przyzębia wskazują, że choroba ta jest wynikiem złożonych interakcji między dysbiozą mikrobiomem a dysregulowaną odpowiedzią zapalną organizmu⁴.

Mikrobna dysbioza jako czynnik inicjujący

Głównym czynnikiem etiologicznym zapoczątkowania i progresji zapalenia przyzębia jest biofilm płytki nazębnej, będący zorganizowanym skupiskiem mikroorganizmów występującym w złożonej macierzy międzykomórkowej⁵. Jednak rozwój periodontitis wymaga czegoś więcej niż tylko zwiększenia biomasy płytki nazębnej. Biodfilm nie tylko zawiera patogeny, ale także bakterie symbiotyczne, które w warunkach homeostazy utrzymują zrównoważoną relację między mikrobiomem płytki a odpowiedzią immunologiczno-zapalną gospodarza⁶.

Przejście od zdrowia przyzębia do zaawansowanych stadiów zapalenia przyzębia wiąże się z przesunięciem mikrobiologicznym od dominacji bakterii symbiotycznych (symbionty) do dysbiozy, z wysokim odsetkiem bakterii patogennych, tzw. patobiontów⁷. Mikroorganizmy, takie jak Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia i Treponema denticola, znane jako kompleks czerwony, są kluczowymi patogenami w patogenezie zapalenia przyzębia⁸⁹.

Szczególną rolę przypisuje się P. gingivalis, który nawet w niskich stężeniach może inicjować chorobę przyzębia poprzez zmianę składu całej społeczności mikrobiologicznej i wywołanie dysbiozy bakteryjnej¹⁰. Bakteria ta posiada liczne czynniki wirulencji, w tym kapsuła, białka błony zewnętrznej, LPS, hemaglutyniny, fimbrie i gingipainy, które są niezbędne do kolonizacji, przetrwania, unikania układu odpornościowego gospodarza i indukcji zapalenia¹¹¹².

Najnowsze badania wykazały, że bakterie periodontologiczne wykształciły złożone mechanizmy unikania odpowiedzi immunologicznej. Odkryto, że P. gingivalis wykorzystuje białko CD47 do zakłócania odpowiedzi immunologicznej organizmu. CD47, znane jako sygnał „nie jedz mnie” w komórkach nowotworowych, odgrywa kluczową rolę w ochronie P. gingivalis przed zniszczeniem przez komórki immunologiczne¹³.

Odpowiedź immunologiczna i zapalna gospodarza

Patogeneza zapalenia przyzębia obejmuje elementy zarówno odporności wrodzonej, jak i adaptacyjnej¹⁴. Odpowiedź immunologiczna gospodarza na poddziąsłowy biofilm związany z zębem może być potencjalnie ochronna, utrzymując zrównoważone interakcje gospodarz-mikrob i zdrowe przyzębie (homeostaza tkankowa). Jednak u osób z podatnością na zapalenie przyzębia odpowiedź gospodarza jest nieskuteczna, dysregulowana i destrukcyjna¹⁵.

Pierwotna odpowiedź na patogeny w układzie odporności wrodzonej jest wyzwalana przez receptory rozpoznające wzorce (Pattern Recognition Receptors – PRRs), które wiążą molekularne wzorce związane z patogenami (Pathogen-Associated Molecular Patterns – PAMPs)¹⁶. W odpowiedzi na bakteryjny LPS, różne komórki produkują IL-1, TNF-α i PGE2, co prowadzi do aktywacji, proliferacji i różnicowania osteoklastów¹⁷.

Komórki nabłonkowe wytwarzają IL-8 i ICAM-1 w odpowiedzi na antygeny bakteryjne. Te czynniki chemotaktyczne rekrutują neutrofile do szczeliny dziąsłowej. Neutrofile kontrolują atak bakteryjny poprzez fagocytozę, ale również wydzielają metaloproteinazy macierzy lub kolagenazy (MMP-8), co prowadzi do degradacji kolagenu¹⁸.

W miarę postępu zapalenia przyzębia limfocyty adaptacyjnego układu odpornościowego naciekają tkanki przyzębia, uwalniając mediatory molekularne zapalne i immunologiczne, które zmieniają równowagę metabolizmu kości, wyznaczając przejście od zapalenia dziąseł do zapalenia przyzębia¹⁹.

Szczególną rolę przypisuje się komórkom Th17, które stanowią główne źródło IL-17A u ludzi i w modelach zwierzęcych zapalenia przyzębia. Ich akumulacja w tkankach dziąsłowych jest zależna od IL-6, a różnicowanie Th17 i ekspresja IL-17A są ściśle regulowane przez przekaźnik sygnału i aktywator transkrypcji-3 (STAT3)²⁰.

Mechanizmy destrukcji tkanek

W zapaleniu przyzębia, zniszczenie tkanek przyzębia jest powszechnie uznawane za wynik odpowiedzi immunologiczno-zapalnej gospodarza wywołanej przez mikroorganizmy przyzębia²¹. Chociaż bakterie są niezbędne do patogenezy choroby, to głównie odpowiedź zapalna gospodarza na to wyzwanie mikrobiologiczne może ostatecznie wyrządzić szkody w tkankach przyzębia²².

Kluczowym czynnikiem w patogenezie zapalenia przyzębia jest trójskładnikowy układ białek składający się z receptora aktywatora czynnika jądrowego-κB ligand (RANKL), jego funkcjonalnego receptora RANK i jego receptora pułapkowego osteoprotegeryny (OPG)²³. W zapaleniu przyzębia, zwiększenie stosunku RANKL/OPG sprzyja rekrutacji prekursorów osteoklastów, ich fuzji i późniejszej aktywacji, prowadząc do resorpcji kości²⁴.

Cytokiny, takie jak IL-1, TNF, IL-6, czynnik stymulujący kolonie makrofagów (M-CSF), IL-17 i PGE2, należą do ważniejszych mediatorów prozapalnych, które stymulują aktywację osteoklastów²⁵. Głównym szlakiem, poprzez który mediator zapalny PGE2 stymuluje resorpcję kości, jest regulacja w górę ekspresji RANKL i hamowanie ekspresji OPG w komórkach osteoblastycznych²⁶.

W kontekście zapalenia przyzębia, podwyższone poziomy RANKL i obniżone poziomy OPG wykryto w próbkach płynu dziąsłowego u pacjentów z zapaleniem przyzębia, a stosunek RANKL/OPG został zaproponowany jako potencjalny biomarker do wykrywania destrukcji kości²⁷.

Rola metaloproteinaz macierzy (MMPs)

Metaloproteinazy macierzy (MMPs) są zależnymi od wapnia endopeptydazami, które degradują białka macierzy pozakomórkowej. Ich nadekspresja, niedoregulowanie lub polimorfizmy genów mogą być kluczowe w przewlekłym zapaleniu, takim jak zapalenie przyzębia²⁸.

Dominującymi MMPs w zapaleniu przyzębia są MMP-8 i MMP-9, które są wydzielane przez neutrofile i są bardzo skuteczne w degradacji kolagenu typu I, najobfitszego typu w więzadle przyzębia²⁹. Interakcja między zapaleniem przyzębia a uporczywym zakażeniem bakteryjnym zwiększa ekspresję i aktywność neutralnych proteinaz, zwłaszcza z rodziny metaloproteinaz macierzy, co przyczynia się do postępującego rozkładu tkanki podporowej przyzębia³⁰.

Badania wykazały, że leki hamujące MMP (MMPI), takie jak doksycyklina, mogą być stosowane jako leki wspomagające w celu wzmocnienia zarówno skaling, jak i kiretaż korzeni w leczeniu zapalenia przyzębia miejscowo oraz w celu zmniejszenia zapalenia ogólnoustrojowo³¹.

Mechanizmy epigenetyczne w patogenezie zapalenia przyzębia

Ekspresja genów jest modulowana przez różne mechanizmy epigenetyczne, takie jak metylacja DNA, modyfikacje histonów lub aktywność niekodującego RNA. Te procesy mogą być również indukowane przez patogeny związane z zapaleniem przyzębia³².

Aberracyjne profile metylacji promotora genów zaangażowanych w aktywację zapalną, w tym TLR2, PTGS2, IFNG, IL6, IL8 i TNF, obserwowano w tkance dziąsłowej, krwi obwodowej lub błonie śluzowej policzka pacjentów z zapaleniem przyzębia, korelując ze zmianami w ekspresji i ciężkością choroby³³.

Ekspresja enzymów regulujących acetylację histonów, w szczególności deacetylaz histonów (HDAC), jest również dysregulowana w tkance dziąsłowej dotkniętej zapaleniem przyzębia. Zakażenie komórek nabłonka dziąsłowego, fibroblastów dziąsłowych i komórek więzadła przyzębia patogenami jamy ustnej Porphyromonas gingivalis lub Treponema denticola indukuje zmiany w ekspresji i aktywności enzymów modyfikujących chromatynę, a także lokalne i globalne zmiany w profilach metylacji DNA oraz w markerach acetylacji i metylacji histonów³⁴.

Te zmiany epigenetyczne są związane z nadmierną produkcją cytokin prozapalnych, chemokin i enzymów degradujących macierz, które mogą być hamowane przez małe cząsteczki inhibitorów HDAC (HDACi) lub metylotransferaz DNA³⁵.

Modele patogenezy zapalenia przyzębia

Modele patogenezy pomagają w integracji danych dostępnych z aktualnych badań naukowych, które pomagają w kompleksowym zrozumieniu choroby. Zapalenie przyzębia jest złożoną chorobą z zawiłymi interakcjami między różnymi komponentami, z których każdy przyczynia się do dynamicznego charakteru procesu chorobowego³⁶.

Model liniowy wskazywał, że złogi bakteryjne są głównym i kluczowym czynnikiem w patogenezie chorób przyzębia.
Model klasyczny obejmuje współdziałanie bakterii z czynnikami odpornościowymi gospodarza, wraz z zestawem środowiskowych i nabytych czynników ryzyka, w tym genetyką, w patogenezie zapalenia przyzębia.
Model biologiczny systemów uwzględnia wszystkie komponenty, które przyczyniają się do końcowego fenotypu klinicznego w postaci nałożonego diagramu Venna, który przedstawia nakładające się relacje i interakcje między różnymi czynnikami.
Model synergii i dysbiozy polimikrobowej (PSD) podkreśla, że zapalenie przyzębia jest spowodowane przez grupę synergistycznych i dysbiotycznych społeczności mikrobowych organizmów autochtonicznych działających w sposób skoordynowany.³⁷

Najnowszy model polimikrobowej dysbiozy genetycznej obejmuje synergię polimikrobową w określonym środowisku, ekspresję genów dysbiotycznych mikrobiów oraz genetyczną podatność gospodarza, aby uwzględnić złożoność chorób przyzębia³⁸.

Rola czynników genetycznych w patogenezie

Wiele badań wykazało, że polimorfizmy genetyczne mogą zwiększać podatność na zapalenie przyzębia³⁹. Etiologia jest złożona i wieloczynnikowa, obejmująca czynniki genetyczne i niegenetyczne środowiskowe. Jednak nie jest jasne, w jaki sposób określana jest genetyczna podatność na zapalenie przyzębia⁴⁰.

Wiele badań skupiło się na roli polimorfizmów genu interleukiny 4, zwłaszcza 590C/T i 33 C/T, oraz ich związku z przewlekłym zapaleniem przyzębia. Polimorfizm IL-4 590 C/T zwiększał ryzyko przewlekłego zapalenia przyzębia w badaniach z Niemiec, Brazylii i Chin, podczas gdy polimorfizm IL-4 33 C/T okazał się ochronny dla przewlekłego zapalenia przyzębia w badaniu populacji indyjskiej⁴¹.

Drugim intensywnie badanym czynnikiem genetycznym są polimorfizmy receptorów toll-podobnych TLR2 i TLR4. Niektóre z nich zwiększają ryzyko przewlekłego zapalenia przyzębia. Zaobserwowano autosomalny recesywny wzór dziedziczenia dla przewlekłego zapalenia przyzębia w polimorfizmach TLR4 C/G (rs7873784) i TLR4 299 A/G⁴².

Zapalenie przyzębia a choroby ogólnoustrojowe

Zapalenie przyzębia może powodować utratę zębów, a bakterie wywołujące zapalenie przyzębia mogą przedostawać się do krwiobiegu przez tkankę dziąsłową, potencjalnie wpływając na inne części ciała. Na przykład, zapalenie przyzębia jest powiązane z chorobami układu oddechowego, reumatoidalnym zapaleniem stawów, chorobą wieńcową, przedwczesnym porodem i niską masą urodzeniową oraz problemami z kontrolą poziomu cukru we krwi w cukrzycy⁴³.

Mimo że inwazyjna P. gingivalis jest związana z różnymi formami chorób sercowo-naczyniowych, w tym udarem, chorobą wieńcową, migotaniem przedsionków i niewydolnością serca, najlepsze dowody na bezpośredni związek przyczynowy istnieją między inwazyjną P. gingivalis (chorobą przyzębia) a miażdżycą. Badania in vivo i in vitro na modelach zwierzęcych wykazały, że fimbrie P. gingivalis promują wnikanie do komórek gospodarza i tworzenie zmian aterozakrzepowych po przedostaniu się bakterii do krwiobiegu, na przykład przez zmiany w jamie ustnej⁴⁴.

Pętla samopodtrzymująca w zapaleniu przyzębia

Zapalenie przyzębia powstaje w wyniku zakłócenia homeostazy gospodarz-mikrob u podatnych osób, prowadzącego do dysbiozy i destrukcyjnego zapalenia, które nie tylko aktywuje osteoklastogenezę i utratę kości, ale także dostarcza składników odżywczych (produkty rozpadu tkanek), które umożliwiają dysbiotycznej mikrobiocie wzrost i przetrwanie⁴⁵.

Zapalenie jest nie tylko konsekwencją dysbiozy, ale poprzez pośredniczenie w dysfunkcji i uszkodzeniu tkanek, napędza dalszy wzrost selektywnie dysbiotycznych społeczności bakterii (inflammofile), generując w ten sposób samopodtrzymującą się pętlę sprzężenia zwrotnego, która utrwala chorobę⁴⁶.

Początkowa odpowiedź zapalna na rozwój biofilmu poddziąsłowego może wybierać inflammofilne bakterie patobiotyczne, które po dalszym wzroście w korzystnym pod względem odżywczym środowisku zapalnym, mogą jeszcze bardziej nasilać zapalenie. Ta pętla sprzężenia zwrotnego dysbiozy i zapalenia może ostatecznie spowodować jawne zapalenie przyzębia u podatnych osób⁴⁷.

Kluczową rolę odgrywają bakterie inflammofilne, czyli te konsorcja mikrobiologiczne związane z zapaleniem przyzębia, które mogą wytrzymać zapalenie i wykorzystywać warunki zapalne do przetrwania i rozwoju, takie jak podwyższenie pH⁴⁸.

Potencjalne strategie terapeutyczne

Zrozumienie mechanizmów patogenezy zapalenia przyzębia otwiera drogę do nowych strategii terapeutycznych. Przyszłe strategie leczenia mogą wykorzystywać rosnącą wiedzę na temat interakcji gospodarz/bakteria i interakcji międzybakteryjnych, aby zapobiegać dysbiozie przyzębia i leczyć zapalenie przyzębia⁴⁹.

Badania prekliniczne wykazały, że farmakologiczne hamowanie Stat3 (z wykorzystaniem inhibitora C188-9, małocząsteczkowego związku zaprojektowanego w celu zapobiegania aktywacji Stat3) zapobiegało utracie kości zapalnej w modelach zapalenia przyzębia⁵⁰.

Hamowanie P. gingivalis przy użyciu inhibitora peptydowego, inhibitorów quorum sensing i inhibitora naturalnego może tłumić czynniki wirulencji i hamować tworzenie biofilmu P. gingivalis, hamując w ten sposób patogenezę zapalenia przyzębia⁵¹.

Badania wykazały, że blokowanie CD47 lub TSP-1 znacznie poprawiło eliminację bakterii przez układ odpornościowy. Myszy pozbawione CD47 wykazywały większą zdolność do eliminacji P. gingivalis, co sugeruje, że celowanie w ten szlak mogłoby zapewnić obiecującą strategię leczenia chorób przyzębia⁵².

Obecne leczenie przyzębia koncentruje się na mechanicznym zmniejszaniu obciążenia bakteryjnego, ale zrozumienie, w jaki sposób te bakterie unikają odpowiedzi immunologicznej, otwiera nowe możliwości terapeutyczne. Celowanie w sygnalizację CD47-TLR2 lub TSP-1 może stanowić nowe podejście do zarządzania przewlekłymi infekcjami związanymi ze zdrowiem jamy ustnej i ogólnoustrojowym⁵³.

Znaczenie patogenezy zapalenia przyzębia

Zrozumienie mechanizmów regulujących patogenezę chorób przyzębia jest decydującym czynnikiem w podejmowaniu skutecznych środków kontroli choroby⁵⁴. Patogeneza zapalenia przyzębia jest wynikiem zakłócenia homeostazy gospodarz-mikrobiom prowadzącego do dysbiozy i destrukcyjnego zapalenia⁵⁵.

Biofilm płytki nazębnej jest niezbędny do rozpoczęcia procesu patologicznego, ale sam nie wyjaśnia różnorodności stadiów choroby. Dlatego pytania dotyczące podatności immunologicznej jednostki mogą być uzupełnieniem odpowiedzi, a planowanie leczenia periodontologicznego powinno opierać się na podstawach naukowych⁵⁶.

Zapalenie przyzębia nie jest uleczalne, ale jest możliwe do opanowania przy odpowiednim leczeniu. Jednym z etapów choroby dziąseł, który jest całkowicie odwracalny, jest zapalenie dziąseł (bardzo wczesna choroba przyzębia). Jeśli wykryjesz zapalenie dziąseł wystarczająco wcześnie, możesz je odwrócić poprzez regularne czyszczenie zębów i skrupulatną higienę jamy ustnej⁵⁷.

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Materiały źródłowe

#1 Periodontal Pathogenesis: Definitions and Historical Perspectives | SpringerLink
https://link.springer.com/chapter/10.1007/978-3-319-53737-5_1
Periodontal disease, or periodontitis, is a globally widespread pathology of the human oral cavity. Indeed, approximately 10% of the global adult population is highly vulnerable to severe periodontitis. Another 10-15% appears to be completely resistant to it, while the remainder vary between these two extremes. […] That means that periodontitis is an inevitable oral pathology of the human population, and its prevalence increases with age. Taking also under consideration the increasing life expectancy, periodontitis is a growing health problem.
#2 Pathogenesis of Periodontal Disease | IntechOpen
https://www.intechopen.com/chapters/67314
Inflammation is a physiological response of the innate immune system against several endogenous or exogenous stimuli. […] The main etiologic factor of periodontal disease is bacteria which substantially harbor the human oral cavity. […] The knowledge of how immune mechanisms and inflammatory responses are regulated is fundamental to understanding the pathogenesis of periodontal disease. […] Periodontitis is a chronic multifactorial disease characterized by an inflammation of the periodontal tissue mediated by the host, which is associated with dysbiotic plaque biofilms, resulting in the progressive destruction of the tooth-supporting apparatus and loss of periodontal attachment. […] The bacterial biofilm formation initiates gingival inflammation; however, periodontitis initiation and progression depend on dysbiotic ecological changes in the microbiome in response to nutrients from gingival inflammatory and tissue breakdown products and anti-bacterial mechanisms that attempt to contain the microbial challenge with in the gingival sulcus area once inflammation has initiated.
#3 Periodontitis – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/periodontitis/symptoms-causes/syc-20354473
Periodontitis is a severe gum infection that can lead to tooth loss, bone loss and other serious health complications. […] Periodontitis (per-e-o-don-TIE-tis), also called gum disease, is a serious gum infection that damages the soft tissue around teeth. Without treatment, periodontitis can destroy the bone that supports your teeth. This can cause teeth to loosen or lead to tooth loss. […] In most cases, the development of periodontitis starts with plaque. Plaque is a sticky film mainly made up of bacteria. If not treated, here’s how plaque can advance over time to periodontitis: […] Ongoing gum irritation and swelling, called inflammation, can cause periodontitis. Eventually this causes deep pockets to form between your gums and teeth. These pockets fill with plaque, tartar and bacteria and become deeper over time. If not treated, these deep infections cause a loss of tissue and bone. Eventually you may lose one or more teeth. Also, ongoing inflammation can put a strain on your immune system, causing other health problems.
#4 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
Recent advances indicate that periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation. […] Inflammation is not only a consequence of dysbiosis but, via mediating tissue dysfunction and damage, fuels further growth of selectively dysbiotic communities of bacteria (inflammophiles), thereby generating a self-sustained feed-forward loop that perpetuates the disease. […] The host immune response to the subgingival tooth-associated biofilm can be potentially protective, thus maintaining balanced host-microbe interactions and a healthy periodontium (tissue homeostasis). […] However, in individuals with susceptibility to periodontitis, the host response is ineffective, dysregulated, and destructive. […] Whereas the bacteria are required for disease pathogenesis, it is predominantly the host inflammatory response to this microbial challenge that can ultimately inflict damage upon the periodontal tissues.
#5 Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC10071981/
The primary etiological agent for the initiation and progression of periodontal disease is the dental plaque biofilm which is an organized aggregation of microorganisms residing within a complex intercellular matrix. […] However, the introduction of sophisticated diagnostic and laboratory assays has led to the realization that the development of periodontitis requires more than a mere increase in the biomass of dental plaque. Indeed, multispecies biofilms exhibit complex interactions between the bacteria and the host. In addition, not all resident microorganisms within the biofilm are pathogenic, since beneficial bacteria exist that serve to maintain a symbiotic relationship between the plaque microbiome and the hosts immune-inflammatory response, preventing the emergence of pathogenic microorganisms and the development of dysbiosis.
#6 Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC10071981/
The primary etiological agent for the initiation and progression of periodontal disease is the dental plaque biofilm which is an organized aggregation of microorganisms residing within a complex intercellular matrix. […] However, the introduction of sophisticated diagnostic and laboratory assays has led to the realization that the development of periodontitis requires more than a mere increase in the biomass of dental plaque. Indeed, multispecies biofilms exhibit complex interactions between the bacteria and the host. In addition, not all resident microorganisms within the biofilm are pathogenic, since beneficial bacteria exist that serve to maintain a symbiotic relationship between the plaque microbiome and the hosts immune-inflammatory response, preventing the emergence of pathogenic microorganisms and the development of dysbiosis.
#7 Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC10071981/
The dental plaque biofilm, alongside other environmental, lifestyle and genetic risk factors, is the main etiological agent responsible for the development and progression of periodontitis. […] In 1994, Marsh suggested that ecological stress was the driver for imbalance in the oral microbiota, encouraging the outgrowth of pathogenic bacteria; this was known as the ecological plaque hypothesis (EPH). […] This work, with the EPH, set the basis to the keystone-pathogen hypothesis, proposed by Hajishengallis and colleagues. This hypothesis explained the shifting of the microbiome from a symbiotic one to a biofilm characterized by dysbiosis induced and aggravated by low abundant keystone pathogens. For example, P. gingivalis elicits an intense/destructive host immune response. […] The process of transition from periodontal health to the advanced stages of periodontitis is associated with a microbial shift from the major symbiotic bacteria known as symbionts to dysbiosis, with high proportions of pathogenic bacteria, the so-called pathobionts.
#8 Virulence Mechanism of Periodontal Bacteria – Experiential Learning Network – University at Buffalo
https://www.buffalo.edu/eln/students/project-portal/host-page.host.html/content/shared/www/eln/project-portal/project-profiles/active-projects/virulence-mechanism-of-periodontal-bacteria.detail.html
Importantly, microbial imbalance known as dysbiosis due to colonization by pathogenic organisms in the subgingival niche (spaces between the gums and teeth) initiates a common disease in adults known as Periodontitis, a chronic condition that if untreated often leads to tooth loss and a contributing risk factor to the progression of many systemic diseases such as cardiovascular diseases and diabetes. […] Colonization by a group of Gram-negative anaerobes Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola – collectively known as the 'red-complex’ – in the subgingival crevices is a major cause of periodontitis. […] Our research focuses on the components of red-complex bacteria that help bacteria to colonize or trigger an inflammatory response detrimental to the gums/tooth supporting tissues.
#9 SciELO Brazil – Host response mechanisms in periodontal diseases Host response mechanisms in periodontal diseases
https://www.scielo.br/j/jaos/a/7YCv9xpKQcXzLfMYVnCFJpB/
Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. […] In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). […] The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them.
#10 Porphyromonas gingivalisâ Role In the Pathogenesis of Periodontal Disease – Decisions in Dentistry
https://decisionsindentistry.com/article/porphyromonas-gingivalis-role-pathogenesis-periodontal-disease/
Acknowledged as one of the most important bacteria in the etiology and pathogenesis of periodontal disease, Porphyromonas gingivalis continues to be extensively studied, not only in periodontal conditions, but also in many systemic diseases based on its ability to infect distant tissues and organs. […] Although able to initiate periodontal disease even when found at low levels in biofilm, P. gingivalis nevertheless requires the presence of other bacteria to cause disease. […] This Gram-negative anaerobe accomplishes this by altering the entire microbial community and triggering bacterial dysbiosis. […] The process by which periodontal pathogens invade and travel through barriers to distant areas of the body is not well understood and is actively being investigated. […] P. gingivalis is rightly termed a keystone pathogen because of its ability to use various deliberate mechanisms to resist, weaken or manipulate host immune responses.
#11 Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC10071981/
The term inflammophilic refers to those microbial consortia associated with periodontitis that can endure inflammation and use inflammatory conditions to survive and prosper, such as elevations in pH. […] This polymicrobial synergism within the dental plaque biofilm not only exists at the nutritional level but inter-microbial metabolic product and gene expression exchanges are necessary to sufficiently increase biomass virulence and induce disease, which cannot be triggered by weakly virulent individual species alone. […] The crucial role of the hosts inflammatory response in changing microbial composition in the subgingival environment is important to recognize. […] The dysbiosis-associated pathogen P. gingivalis exhibits a large arsenal of virulence factors that in presence of nutrients are essential for colonization and persistence, immune system evasion, impairment of inflammatory cell function and induction of immune subversion and consequent inflammation.
#12 Porphyromonas gingivalisâ Role In the Pathogenesis of Periodontal Disease – Decisions in Dentistry
https://decisionsindentistry.com/article/porphyromonas-gingivalis-role-pathogenesis-periodontal-disease/
A groundbreaking study in germ-free mice inoculated with P. gingivalis demonstrated its inability to cause periodontitis alone. […] Considering its many adaptive strategies to maintain virulence, P. gingivalis is truly a microbial enigma. […] P. gingivalis maintains a favorable inflammatory nutrient-rich environment by producing and utilizing its gingipain protease (Arg-gingipain); however, it can transition to using another protease (Lys-gingipain) to ameliorate the negative effects of too great an inflammatory response, highlighting this microbes adaptability to its environment. […] P. gingivalis accomplishes this with the assistance of its potent virulence factors: capsule, outer membrane proteins and vesicles, lipopolysaccharide (LPS), hemagglutinins, fimbriae, gingipains and others.
#13 Azthena logo with the word Azthena
https://www.news-medical.net/news/20250224/Study-uncovers-novel-immune-evasion-mechanism-used-by-key-bacterium-in-periodontitis.aspx
Researchers have identified a new mechanism by which a key bacterium in periodontitis evades the immune system. […] The study reveals that the bacterium exploits the protein CD47 to suppress immune responses, allowing it to persist in inflamed tissues and contribute to systemic diseases. […] A recent study led by Prof. Gabriel Nussbaum from the Faculty of Dental Medicine at the Hebrew University of Jerusalem has uncovered a novel immune evasion mechanism used by Porphyromonas gingivalis (P. gingivalis), a key bacterial culprit behind periodontitis- a severe gum infection. […] The research team found that P. gingivalis exploits the integrin-associated protein CD47 to interfere with the body’s immune response. […] CD47, known as a „don’t eat me” signal in cancer cells, plays a crucial role in protecting P. gingivalis from being destroyed by immune cells.
#14 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
The histopathology of periodontitis involves elements of both innate and adaptive immunity. […] In periodontitis, these complex interactions lead to inflammation-induced bone loss, which is largely mediated by a triad of proteins consisting of the receptor activator of nuclear factor-B ligand (RANKL), its functional receptor RANK, and its decoy receptor osteoprotegerin. […] The ideal outcome of an inflammatory response is its timely termination so that it does not become chronic with potentially adverse effects. […] The successful resolution of inflammation is an active and well-coordinated process that involves a series of steps. […] In this regard, the addition of serum, hemoglobin, or hemin to an in vitro generated oral multispecies community selectively induces the outgrowth of pathobionts, which interestingly upregulate genes that encode proteases, hemolysins, and molecules involved in hemin acquisition.
#15 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
Recent advances indicate that periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation. […] Inflammation is not only a consequence of dysbiosis but, via mediating tissue dysfunction and damage, fuels further growth of selectively dysbiotic communities of bacteria (inflammophiles), thereby generating a self-sustained feed-forward loop that perpetuates the disease. […] The host immune response to the subgingival tooth-associated biofilm can be potentially protective, thus maintaining balanced host-microbe interactions and a healthy periodontium (tissue homeostasis). […] However, in individuals with susceptibility to periodontitis, the host response is ineffective, dysregulated, and destructive. […] Whereas the bacteria are required for disease pathogenesis, it is predominantly the host inflammatory response to this microbial challenge that can ultimately inflict damage upon the periodontal tissues.
#16 SciELO Brazil – Host response mechanisms in periodontal diseases Host response mechanisms in periodontal diseases
https://www.scielo.br/j/jaos/a/7YCv9xpKQcXzLfMYVnCFJpB/
The primary response to pathogens in the innate immune system is triggered by Pattern Recognition Receptors (PRRs) that bind Pathogen-Associated Molecular Patterns (PAMPs), found in a broad type of organisms. […] The recent advancements in the periodontal research field are consistent with a new model of pathogenesis, according to which periodontitis is initiated by a synergistic and dysbiotic microbial community rather than by a select bacterial complex, that is, polymicrobial synergy and dysbiosis model (PSD model). […] The interaction between periodontal inflammation and persistent bacterial infection up-regulates the expression and activity of neutral proteinases, particularly of the matrix metalloproteinase family, which contributes to the progressive breakdown of periodontal supporting tissue.
#17 Pathogenesis of periodontitis | PPT
https://www.slideshare.net/slideshow/pathogenesis-of-periodontitis/57821506
The immune system generally elicits a vigorous inflammation response against pathogens aimed at eliminating them, whereas it normally tolerates commensals. […] In response to bacterial LPS, various cells produce IL-1, TNF-, and PGE2. Production of IL-1, TNF-, and PGE2 leads to osteoclast activation, proliferation and differentiation. […] In a patient susceptible to periodontitis, how does the body react? Epithelial Cells produce IL-8 and ICAM-1 in response to bacteria antigens. IL-8 and ICAM-1 are chemotactic signals for neutrophils, which are recruited to the sulcus. Neutrophils control bacterial assault by phagocytosis but also secrete matrix metalloproteinases or collagenases (MMP-8) which results in collagen degradation. […] Higher amounts of IL-1, TNF-, PGE2, MMPs lead to disease, while lower amounts of IL-10, TGF-, IL-1ra, TIMPs are associated with health.
#18 Pathogenesis of periodontitis | PPT
https://www.slideshare.net/slideshow/pathogenesis-of-periodontitis/57821506
The immune system generally elicits a vigorous inflammation response against pathogens aimed at eliminating them, whereas it normally tolerates commensals. […] In response to bacterial LPS, various cells produce IL-1, TNF-, and PGE2. Production of IL-1, TNF-, and PGE2 leads to osteoclast activation, proliferation and differentiation. […] In a patient susceptible to periodontitis, how does the body react? Epithelial Cells produce IL-8 and ICAM-1 in response to bacteria antigens. IL-8 and ICAM-1 are chemotactic signals for neutrophils, which are recruited to the sulcus. Neutrophils control bacterial assault by phagocytosis but also secrete matrix metalloproteinases or collagenases (MMP-8) which results in collagen degradation. […] Higher amounts of IL-1, TNF-, PGE2, MMPs lead to disease, while lower amounts of IL-10, TGF-, IL-1ra, TIMPs are associated with health.
#19 Pathogenesis of Periodontal Disease | IntechOpen
https://www.intechopen.com/chapters/67314
The primary features of periodontitis include the loss of periodontal tissue support, manifested through clinical attachment loss and radiographically assessed alveolar bone loss, presence of periodontal pocketing, and gingival bleeding. […] The most important characteristic of periodontitis is the inflammatory reabsorption of the tooth-supporting alveolar bone due to the uncontrolled host immune response against periodontal infection, since the destructive events, which lead to the irreversible phenotype of periodontal disease, are the result of the persistence of a chronic and exacerbated inflammatory immune response. […] The inflammatory immune response is triggered by the interaction of resident cells with the bacterial biofilm attached to the tooth surface. […] When the inflammatory response becomes chronic, the lymphocytes of the adaptive immune system invade the periodontal tissues releasing inflammatory and immune molecular mediators, which alter the balance of bone metabolism, marking the transition from gingivitis to periodontitis.
#20 Th17 Cells in Gingival Immunity and Their Key Role in Periodontitis Pathogenesis
https://archive.hshsl.umaryland.edu/handle/10713/7340
Periodontitis is a very common human disease characterized by inflammatory bone destruction in the oral cavity. It affects more than 64 million adults in the United States and is often linked to systemic or distant co-morbidities. T helper (Th) cells and specifically Th17 have been identified as important constituents of the inflammatory lesion in periodontitis. However, the specific role of Th17 cells in periodontitis and whether they drive inflammatory pathology is not fully understood. […] In fact, Th17 cells represent the major source of IL-17A in humans and in animal models of periodontitis and we show that their accumulation in gingival tissues is IL-6 dependent. Th17 differentiation and IL-17A expression are tightly regulated by signal transducer and activator of transcription-3 (STAT3).
#21 Inflammatory mediators in the pathogenesis of periodontitis | Expert Reviews in Molecular Medicine | Cambridge Core
https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/inflammatory-mediators-in-the-pathogenesis-of-periodontitis/05B60424BB7C7B946500A924A8B53453
Periodontitis is a chronic inflammatory condition of the periodontium involving interactions between bacterial products, numerous cell populations and inflammatory mediators. […] It is generally accepted that periodontitis is initiated by complex and diverse microbial biofilms which form on the teeth, i.e. dental plaque. […] As a result of cellular activation, inflammatory mediators, including cytokines, chemokines, arachidonic acid metabolites and proteolytic enzymes collectively contribute to tissue destruction and bone resorption. […] The primary hallmark of periodontitis, the destruction of periodontal tissue, is widely accepted to be a result of the host immune inflammatory response caused by periodontal microorganisms. […] The host response has traditionally been considered to be mediated mainly by B and T lymphocytes, neutrophils and monocytes/macrophages.
#22 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
Recent advances indicate that periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation. […] Inflammation is not only a consequence of dysbiosis but, via mediating tissue dysfunction and damage, fuels further growth of selectively dysbiotic communities of bacteria (inflammophiles), thereby generating a self-sustained feed-forward loop that perpetuates the disease. […] The host immune response to the subgingival tooth-associated biofilm can be potentially protective, thus maintaining balanced host-microbe interactions and a healthy periodontium (tissue homeostasis). […] However, in individuals with susceptibility to periodontitis, the host response is ineffective, dysregulated, and destructive. […] Whereas the bacteria are required for disease pathogenesis, it is predominantly the host inflammatory response to this microbial challenge that can ultimately inflict damage upon the periodontal tissues.
#23 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
The histopathology of periodontitis involves elements of both innate and adaptive immunity. […] In periodontitis, these complex interactions lead to inflammation-induced bone loss, which is largely mediated by a triad of proteins consisting of the receptor activator of nuclear factor-B ligand (RANKL), its functional receptor RANK, and its decoy receptor osteoprotegerin. […] The ideal outcome of an inflammatory response is its timely termination so that it does not become chronic with potentially adverse effects. […] The successful resolution of inflammation is an active and well-coordinated process that involves a series of steps. […] In this regard, the addition of serum, hemoglobin, or hemin to an in vitro generated oral multispecies community selectively induces the outgrowth of pathobionts, which interestingly upregulate genes that encode proteases, hemolysins, and molecules involved in hemin acquisition.
#24 Pathogenesis of Periodontal Disease | IntechOpen
https://www.intechopen.com/chapters/67314
RANKL is a cytokine member of the TNF family that can be bound or secreted to the membrane and stimulates the differentiation of osteoclasts, cell fusion, and activation that leads to bone resorption. […] In periodontitis, the increase in RANKL/OPG promotes the recruitment of osteoclast precursors, their fusion, and subsequent activation, leading to bone resorption.
#25 Inflammatory mediators in the pathogenesis of periodontitis | Expert Reviews in Molecular Medicine | Cambridge Core
https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/inflammatory-mediators-in-the-pathogenesis-of-periodontitis/05B60424BB7C7B946500A924A8B53453
Cytokines such as IL-1, TNF, IL-6, macrophage colony-stimulating factor (M-CSF), IL-17 and PGE2 are among the more important proinflammatory mediators reported to stimulate osteoclast activation. […] The TNF family cytokine RANKL induces the differentiation of osteoclasts in the presence of M-CSF. […] In the context of periodontitis, elevated levels of RANKL and reduced levels of osteoprotegerin (OPG) were detected in the GCF samples of patients with periodontitis and the RANKL/OPG ratio was suggested as a possible biomarker test for detection of bone destruction. […] The major pathway by which the inflammatory mediator PGE2 stimulates bone resorption is generally considered to be via the up-regulation of RANKL expression and the inhibition of OPG expression in osteoblastic cells. […] Cytokines such as TNF, IL-6 and IL-8, which activate multiple signalling cascades including ERK, JNK, NF-B and p38 MAPK are regulated via mRNA stability.
#26 Inflammatory mediators in the pathogenesis of periodontitis | Expert Reviews in Molecular Medicine | Cambridge Core
https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/inflammatory-mediators-in-the-pathogenesis-of-periodontitis/05B60424BB7C7B946500A924A8B53453
Cytokines such as IL-1, TNF, IL-6, macrophage colony-stimulating factor (M-CSF), IL-17 and PGE2 are among the more important proinflammatory mediators reported to stimulate osteoclast activation. […] The TNF family cytokine RANKL induces the differentiation of osteoclasts in the presence of M-CSF. […] In the context of periodontitis, elevated levels of RANKL and reduced levels of osteoprotegerin (OPG) were detected in the GCF samples of patients with periodontitis and the RANKL/OPG ratio was suggested as a possible biomarker test for detection of bone destruction. […] The major pathway by which the inflammatory mediator PGE2 stimulates bone resorption is generally considered to be via the up-regulation of RANKL expression and the inhibition of OPG expression in osteoblastic cells. […] Cytokines such as TNF, IL-6 and IL-8, which activate multiple signalling cascades including ERK, JNK, NF-B and p38 MAPK are regulated via mRNA stability.
#27 Inflammatory mediators in the pathogenesis of periodontitis | Expert Reviews in Molecular Medicine | Cambridge Core
https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/inflammatory-mediators-in-the-pathogenesis-of-periodontitis/05B60424BB7C7B946500A924A8B53453
Cytokines such as IL-1, TNF, IL-6, macrophage colony-stimulating factor (M-CSF), IL-17 and PGE2 are among the more important proinflammatory mediators reported to stimulate osteoclast activation. […] The TNF family cytokine RANKL induces the differentiation of osteoclasts in the presence of M-CSF. […] In the context of periodontitis, elevated levels of RANKL and reduced levels of osteoprotegerin (OPG) were detected in the GCF samples of patients with periodontitis and the RANKL/OPG ratio was suggested as a possible biomarker test for detection of bone destruction. […] The major pathway by which the inflammatory mediator PGE2 stimulates bone resorption is generally considered to be via the up-regulation of RANKL expression and the inhibition of OPG expression in osteoblastic cells. […] Cytokines such as TNF, IL-6 and IL-8, which activate multiple signalling cascades including ERK, JNK, NF-B and p38 MAPK are regulated via mRNA stability.
#28 The Genetic Aspects of Periodontitis Pathogenesis and the Regenerative Properties of Stem Cells
https://www.mdpi.com/2073-4409/13/2/117
Dysregulated IL-17 could take part in the pathogenesis of PD as well, as this cytokine can enhance inflammation and promote osteoclast formation. […] Prostaglandin-endoperoxide synthase-2 (PTGS2), also known as cyclooxygenase-2 (COX-2), is an enzyme responsible for creating prostaglandin E2 (PGE2) from arachidonic acid. PGE2 is heavily expressed during inflammation, and its levels are increased in GCF. […] Genetic polymorphism in the -765 region has been found to impact the occurrence of PD. […] Matrix metalloproteinases (MMPs) are calcium-dependent endopeptidases that degrade extracellular matrix proteins. […] Their overexpression, under-regulation, or gene polymorphisms may be crucial in chronic inflammation, such as PD. […] The pathogenesis of PD is associated with dysbiosis and inadequate immune reactions, leading to chronic inflammation.
#29 Periodontal pathogenesis | PPT
https://www.slideshare.net/slideshow/periodontal-pathogenesis/75752472
Periodontal pathogenesis, inflammatory process, types of inflammation, mechanism of inflammatory reaction, inflammatory mediators […] Pathogenesis is defined as the origination and development of a disease. It is a step-by-step process that leads to the development of a disease, resulting in a series of changes in the structure and function. It is the process by which the etiologic factor causes the disease. […] Even in the gingival that appear clinically normal there is a chronic low-grade challenge presented by sub-gingival plaque bacteria. Essential mechanism to combat the microbial challenge to prevent bacteria and their products from infiltrating tissues. But an excessive, dysregulated, immune-inflammatory response for a given bacterial challenge leading to increased tissue breakdown. […] This has great relevance in periodontal pathogenesis, as the widened permit migration of neutrophils and macrophages from the gingival connective tissue to enter sulcus to phagocytose bacteria, as well as ingress of bacterial products as well as antigens. […] The bacteria are important because they drive and perpetuate the inflammation but they are responsible for a relatively small proportion of tissue damage. […] Majority of the tissue damage in periodontitis derives from the excessive and dysregulated production of a variety of inflammatory mediators and enzymes which are broadly classified as follows:- CYTOKINES PROSTAGLNDINS MATRIXMETALLOPROTEINASES […] Cytokines play a fundamental role in inflammation and are key inflammatory mediators in periodontal disease. […] The predominant MMPs in periodontitis, MMP-8 and MMP-9 are secreted by neutrophils and are very effective in degrading type I collagen, the most abundant type in the PDL. […] If inflammation becomes more extensive because of increase in bacterial challenge Increased vascular permeability, vasodilatation leading to edema, erythema. […] A cycle of chronic inflammation sets in, characterized by leucocytes, release of inflammatory mediators and destructive enzymes, connective tissue breakdown and proliferation of epithelium, in apical direction. […] This model implies that the presence of plaque bacteria does not inevitably lead to tissue destruction and is supported by a large number of epidemiologic studies, which confirm that more advanced disease is usually confined to a minority of the population.
#30 SciELO Brazil – Host response mechanisms in periodontal diseases Host response mechanisms in periodontal diseases
https://www.scielo.br/j/jaos/a/7YCv9xpKQcXzLfMYVnCFJpB/
The primary response to pathogens in the innate immune system is triggered by Pattern Recognition Receptors (PRRs) that bind Pathogen-Associated Molecular Patterns (PAMPs), found in a broad type of organisms. […] The recent advancements in the periodontal research field are consistent with a new model of pathogenesis, according to which periodontitis is initiated by a synergistic and dysbiotic microbial community rather than by a select bacterial complex, that is, polymicrobial synergy and dysbiosis model (PSD model). […] The interaction between periodontal inflammation and persistent bacterial infection up-regulates the expression and activity of neutral proteinases, particularly of the matrix metalloproteinase family, which contributes to the progressive breakdown of periodontal supporting tissue.
#31
https://scispace.com/papers/effects-of-vitamin-c-local-application-on-ligature-induced-425878ebx7
Evidence is provided on the detrimental role of AGE accumulation in oral cavity tissues and their associated signaling pathways in periodontitis and peri-implantitis to further highlight the significance of oral or topical use of AGE blockers or inhibitors along with dental biofilms removal and DM regulation in patients management. […] The role of reactive oxygen and antioxidant species in periodontal tissue destruction. […] Emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontococcal inflammation, and periodontal inflammation negatively affecting glycaemic control is supported. […] MMP inhibitor (MMPI) drugs, such as doxycycline, can be used as adjunctive medication to augment both the scaling and root planing treatment of periodontitis locally and to reduce inflammation systematically. […] Reactive oxygen species and antioxidant mechanisms in the pathogenesis of periodontitis.
#32 The Genetic Aspects of Periodontitis Pathogenesis and the Regenerative Properties of Stem Cells
https://www.mdpi.com/2073-4409/13/2/117
Periodontitis (PD) is a prevalent and chronic inflammatory disease with a complex pathogenesis, and it is associated with the presence of specific pathogens, such as Porphyromonas gingivalis. Dysbiosis and dysregulated immune responses ultimately lead to chronic inflammation as well as tooth and alveolar bone loss. […] Multiple studies have demonstrated that genetic polymorphisms may increase the susceptibility to PD. Furthermore, gene expression is modulated by various epigenetic mechanisms, such as DNA methylation, histone modifications, or the activity of non-coding RNA. These processes can also be induced by PD-associated pathogens. […] Periodontitis is a state of permanent inflammation in the periodontium. Microbial biofilm and their metabolism cause host cell death and increased turnover, and increased regeneration affects defense responses and epigenetic alterations.
#33 Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential | Clinical Epigenetics | Full Text
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00982-7
Epigenetic mechanisms, namely DNA and histone modifications, are critical regulators of immunity and inflammation which have emerged as potential targets for immunomodulating therapies. […] The prevalence and significant morbidity of periodontitis, in combination with accumulating evidence that genetic, environmental and lifestyle factors cannot fully explain the susceptibility of individuals to disease development, have driven interest in epigenetic regulation as an important factor in periodontitis pathogenesis. […] Aberrant promoter methylation profiles of genes involved in inflammatory activation, including TLR2, PTGS2, IFNG, IL6, IL8, and TNF, have been observed in the gingival tissue, peripheral blood or buccal mucosa from patients with periodontitis, correlating with changes in expression and disease severity.
#34 Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential | Clinical Epigenetics | Full Text
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00982-7
The expression of enzymes that regulate histone acetylation, in particular histone deacetylases (HDACs), is also dysregulated in periodontitis-affected gingival tissue. […] Infection of gingival epithelial cells, gingival fibroblasts and periodontal ligament cells with the oral pathogens Porphyromonas gingivalis or Treponema denticola induces alterations in expression and activity of chromatin-modifying enzymes, as well as site-specific and global changes in DNA methylation profiles and in histone acetylation and methylation marks. […] These epigenetic changes are associated with excessive production of inflammatory cytokines, chemokines, and matrix-degrading enzymes that can be suppressed by small molecule inhibitors of HDACs (HDACi) or DNA methyltransferases. […] The integration of functional studies with global analyses of the epigenetic landscape will provide critical information on the therapeutic and diagnostic potential of epigenetics in periodontal disease.
#35 Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential | Clinical Epigenetics | Full Text
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00982-7
The expression of enzymes that regulate histone acetylation, in particular histone deacetylases (HDACs), is also dysregulated in periodontitis-affected gingival tissue. […] Infection of gingival epithelial cells, gingival fibroblasts and periodontal ligament cells with the oral pathogens Porphyromonas gingivalis or Treponema denticola induces alterations in expression and activity of chromatin-modifying enzymes, as well as site-specific and global changes in DNA methylation profiles and in histone acetylation and methylation marks. […] These epigenetic changes are associated with excessive production of inflammatory cytokines, chemokines, and matrix-degrading enzymes that can be suppressed by small molecule inhibitors of HDACs (HDACi) or DNA methyltransferases. […] The integration of functional studies with global analyses of the epigenetic landscape will provide critical information on the therapeutic and diagnostic potential of epigenetics in periodontal disease.
#36
https://journals.lww.com/jisp/fulltext/2022/26030/models_of_periodontal_disease_pathogenesis__a.4.aspx
Models of pathogenesis help in integrating the data available from current scientific research, which aid in comprehensive understanding of the disease. […] Periodontitis is a complex disease with intricate interactions between various components, each contributing to the dynamic nature of the disease process. […] The linear model implicated that bacterial deposits are a primary and crucial factor in the pathogenesis of periodontal diseases. […] This was the first systematic model to describe the temporal development of host response events leading to the development of periodontitis. […] The hallmark of this model is that it illustrates the distinct roles of microbes and the interaction with host response in periodontal disease pathogenesis. […] The critical pathway model was the first nonlinear model to explain such an association.
#37
https://journals.lww.com/jisp/fulltext/2022/26030/models_of_periodontal_disease_pathogenesis__a.4.aspx
The classical model incorporates the coaction of bacteria with host immune factors, along with an assortment of environmental, and acquired risk factors including genetics, in the pathogenesis of periodontitis. […] The biologic systems model incorporates all components that contribute to the final clinical phenotype into a stacked Venn diagram, which depicts the overlapping relationships and interactions among different factors. […] Periodontal disease is a complex disease and its complexity involves multiple causal components which interplay with each other simultaneously. […] This model elucidates the contribution of Keystone pathogens, in the development of periodontal disease. […] The fundamental tenet of this model is that periodontitis is caused by a group of synergistic and dysbiotic microbial communities of indigenous organisms working in concert.
#38
https://journals.lww.com/jisp/fulltext/2022/26030/models_of_periodontal_disease_pathogenesis__a.4.aspx
The revised model underscores the paradigm shift, from the primary role of bacteria in periodontal disease to bacterial colonization as a secondary event to inflammation. […] This model is based on the conceptual framework that periodontitis is a result of disruption of host-microbiome homeostasis. […] A healthy periodontal state is characterized by a symbiotic biofilm which triggers a proportionate and resolving host response. […] The evolution of the periodontal disease pathogenesis paradigm to a polymicrobial genetic dysbiosis model includes the polymicrobial synergy in a specific environment, the microbial dysbiotic gene expression, and the host genetic susceptibility to encompass the complexity of the periodontal diseases. […] The Page and Schroeder model proposed in 1976 provided a histopathologic roadmap to the pathologic events leading to clinical outcomes.
#39 The Genetic Aspects of Periodontitis Pathogenesis and the Regenerative Properties of Stem Cells
https://www.mdpi.com/2073-4409/13/2/117
Periodontitis (PD) is a prevalent and chronic inflammatory disease with a complex pathogenesis, and it is associated with the presence of specific pathogens, such as Porphyromonas gingivalis. Dysbiosis and dysregulated immune responses ultimately lead to chronic inflammation as well as tooth and alveolar bone loss. […] Multiple studies have demonstrated that genetic polymorphisms may increase the susceptibility to PD. Furthermore, gene expression is modulated by various epigenetic mechanisms, such as DNA methylation, histone modifications, or the activity of non-coding RNA. These processes can also be induced by PD-associated pathogens. […] Periodontitis is a state of permanent inflammation in the periodontium. Microbial biofilm and their metabolism cause host cell death and increased turnover, and increased regeneration affects defense responses and epigenetic alterations.
#40 Scholarly Commons – Excellence Day: Role of Genetics in Pathogenesis of Periodontitis
https://scholarlycommons.pacific.edu/excellence-day/2019/events/52/
Periodontitis is a chronic bacterial inflammatory disease that affects tissues supporting the teeth. It can result in irreversible loss of periodontal attachment and destruction of adjacent alveolar bone leading to increased tooth mobility and finally to exfoliation. Etiology is complex and multifactorial including genetic and non-genetic environmental factors. […] However, it is not clear how a genetic susceptibility to periodontitis is determined. Families with several individuals suffering from aggressive periodontitis are not rare. When life style habits and nutritional factors are excluded as major etiological factors, a genetic background shared with close relatives and passed over generations becomes an important factor. […] Many studies focused on role of interleukin 4 gene polymorphisms, especially 590C/T and 33 C/T and their association with CP. Polymorphism IL-4 590 C/T increased risk for CP in studies from Germany, Brazil, and China, while polymorphism IL-4 33 C/T was found protective for CP in a study from Indian population.
#41 Scholarly Commons – Excellence Day: Role of Genetics in Pathogenesis of Periodontitis
https://scholarlycommons.pacific.edu/excellence-day/2019/events/52/
Periodontitis is a chronic bacterial inflammatory disease that affects tissues supporting the teeth. It can result in irreversible loss of periodontal attachment and destruction of adjacent alveolar bone leading to increased tooth mobility and finally to exfoliation. Etiology is complex and multifactorial including genetic and non-genetic environmental factors. […] However, it is not clear how a genetic susceptibility to periodontitis is determined. Families with several individuals suffering from aggressive periodontitis are not rare. When life style habits and nutritional factors are excluded as major etiological factors, a genetic background shared with close relatives and passed over generations becomes an important factor. […] Many studies focused on role of interleukin 4 gene polymorphisms, especially 590C/T and 33 C/T and their association with CP. Polymorphism IL-4 590 C/T increased risk for CP in studies from Germany, Brazil, and China, while polymorphism IL-4 33 C/T was found protective for CP in a study from Indian population.
#42 Scholarly Commons – Excellence Day: Role of Genetics in Pathogenesis of Periodontitis
https://scholarlycommons.pacific.edu/excellence-day/2019/events/52/
The second intensively studied genetic factor are polymorphisms of toll-like receptors TLR2 and TLR4. Some of them were shown to increase risk for CP. An autosomal recessive pattern of inheritance was observed for CP in TLR4 C/G (rs7873784) and TLR4 299 A/G polymorphisms. While the TLR4 299A/G was found to increase risk for CP, the TLR4 399 C/T seemed to be protective for AP. […] Genetics in periodontics is important and highly researched field. Many studies published in recent years support the evidence that gene polymorphisms influence initiation and progression of periodontal disease on an individual basis. Although association between different candidate gene polymorphisms and its periodontal effects is still very controversial, it appears that several gene polymorphisms can be analyzed and the diagnosed genotypes can be taken into account when a treatment plan is designed.
#43 Periodontitis – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/periodontitis/symptoms-causes/syc-20354473
Periodontitis can cause tooth loss. The bacteria that cause periodontitis can enter your bloodstream through gum tissue, possibly affecting other parts of your body. For example, periodontitis is linked with respiratory disease, rheumatoid arthritis, coronary artery disease, preterm birth and low birth weight, and problems controlling blood sugar in diabetes.
#44 Porphyromonas gingivalis – Wikipedia
https://en.wikipedia.org/wiki/Porphyromonas_gingivalis
Both chronic systemic inflammation and oxidative stress are factors associated with the onset of cardiovascular disease, and are proposed mechanisms by which periodontal disease may, if it indeed is causationally linked to cardiovascular disease, accelerate the disease process of a cardiovascular disease. […] While invasive P. gingivalis is associated with various forms of cardiovascular disease, including stroke, coronary artery disease, atrial fibrillation, and heart failure, the best evidence of a direct causational link is between invasive P. gingivalis (periodontal disease) and atherosclerosis. […] In vivo and in vitro animal models have found that the fimbriae of P. gingivalis promote host cell entry and atherothrombotic lesion formation once the bacteria enter the bloodstream, such as through lesions in the mouth. P. gingivalis has been shown to accelerate the atherosclerosis disease pathway in mice, as well as being found in human atherosclerotic plaque lesions.
#45 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
Periodontitis arises from the disruption of host-microbe homeostasis in susceptible individuals leading to dysbiosis and destructive inflammation that not only activates osteoclastogenesis and bone loss but also provides nutrients (tissue breakdown products) that enable the dysbiotic microbiota to grow and persist. […] Periodontitis is associated with dysbiosis, i.e., an alteration in the abundance or influence of individual species within the polymicrobial community, relative to their abundance or influence in health. […] An initial inflammatory response to subgingival biofilm development may select for inflammophilic pathobiotic bacteria, which, upon further growth in a nutritionally favorable inflammatory environment, can further exacerbate inflammation. […] This feed-forward loop of dysbiosis and inflammation can ultimately cause overt periodontitis in susceptible individuals.
#46 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
Recent advances indicate that periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation. […] Inflammation is not only a consequence of dysbiosis but, via mediating tissue dysfunction and damage, fuels further growth of selectively dysbiotic communities of bacteria (inflammophiles), thereby generating a self-sustained feed-forward loop that perpetuates the disease. […] The host immune response to the subgingival tooth-associated biofilm can be potentially protective, thus maintaining balanced host-microbe interactions and a healthy periodontium (tissue homeostasis). […] However, in individuals with susceptibility to periodontitis, the host response is ineffective, dysregulated, and destructive. […] Whereas the bacteria are required for disease pathogenesis, it is predominantly the host inflammatory response to this microbial challenge that can ultimately inflict damage upon the periodontal tissues.
#47 Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy
https://pmc.ncbi.nlm.nih.gov/articles/PMC7457922/
Periodontitis arises from the disruption of host-microbe homeostasis in susceptible individuals leading to dysbiosis and destructive inflammation that not only activates osteoclastogenesis and bone loss but also provides nutrients (tissue breakdown products) that enable the dysbiotic microbiota to grow and persist. […] Periodontitis is associated with dysbiosis, i.e., an alteration in the abundance or influence of individual species within the polymicrobial community, relative to their abundance or influence in health. […] An initial inflammatory response to subgingival biofilm development may select for inflammophilic pathobiotic bacteria, which, upon further growth in a nutritionally favorable inflammatory environment, can further exacerbate inflammation. […] This feed-forward loop of dysbiosis and inflammation can ultimately cause overt periodontitis in susceptible individuals.
#48 Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC10071981/
The term inflammophilic refers to those microbial consortia associated with periodontitis that can endure inflammation and use inflammatory conditions to survive and prosper, such as elevations in pH. […] This polymicrobial synergism within the dental plaque biofilm not only exists at the nutritional level but inter-microbial metabolic product and gene expression exchanges are necessary to sufficiently increase biomass virulence and induce disease, which cannot be triggered by weakly virulent individual species alone. […] The crucial role of the hosts inflammatory response in changing microbial composition in the subgingival environment is important to recognize. […] The dysbiosis-associated pathogen P. gingivalis exhibits a large arsenal of virulence factors that in presence of nutrients are essential for colonization and persistence, immune system evasion, impairment of inflammatory cell function and induction of immune subversion and consequent inflammation.
#49 Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC10071981/
These events pave the way for overgrowth of inflammophilic pathobionts and provide protection for P. gingivalis from the inflammatory response. […] Future treatment strategies could exploit the growing knowledge of host/bacterial and interbacterial interactions to prevent periodontal dysbiosis and treat periodontitis.
#50 Th17 Cells in Gingival Immunity and Their Key Role in Periodontitis Pathogenesis
https://archive.hshsl.umaryland.edu/handle/10713/7340
We find that AD-HIES patients have reduced susceptibility to periodontitis and present minimal oral inflammation, consistent with blunted Th17 tissue responses. […] These results demonstrate the key role of Th17 in periodontitis and suggest inhibition of Th17 through Stat3 in the treatment/prevention of disease. Indeed, we performed preclinical studies of Stat3 inhibition (using C188-9 inhibitor, a small-molecule compound designed to prevent Stat3 activation) and demonstrated that pharmacologic inhibition of Stat3 prevented inflammatory bone loss in periodontitis models. Our work uncovers the pathogenic potential of Th17 cells in periodontal inflammatory bone loss and suggests pharmacologic inhibition through STAT3 in the prevention of this common inflammatory disease.
#51 Mechanism of inhibiting periodontitis pathogenesis with various variations of inhibitors on Porphyromonas gingivalis: Systematic literature review
https://wjarr.com/content/mechanism-inhibiting-periodontitis-pathogenesis-various-variations-inhibitors-porphyromonas
Periodontitis involves complex interactions between specific pathogenic bacteria and host immune response. […] Inhibition of Porphyromonas gingivalis virulence is one way to prevent periodontitis. […] The use of SAPP as a peptide inhibitor can inhibit the activity of Porphyromonas gingivalis gingipains, suppressing cytokine levels and inhibit colonization of Porphyromonas gingivalis. […] The use of furanone, D-ribose and BMK-Q101 as quorum sensing inhibitors can reduce Porphyromonas gingivalis in biofilms, inhibit the biosynthesis of autoinducer-2 so as to suppress the virulence factors of Porphyromonas gingivalis. […] The use of prenyl flavonoid as a natural inhibitor is a potent inhibitor of Arg-gingipain (Rgp) and Lys-gingipain (Kgp) and completely suppress the growth of Porphyromonas gingivalis. […] Inhibition of Porphyromonas gingivalis using peptide inhibitor, quorum sensing inhibitors and natural inhibitor can suppress virulence factors and inhibit biofilm formation of Porphyromonas gingivalis thus inhibiting the pathogenesis of periodontitis.
#52 Azthena logo with the word Azthena
https://www.news-medical.net/news/20250224/Study-uncovers-novel-immune-evasion-mechanism-used-by-key-bacterium-in-periodontitis.aspx
Our findings suggest that P. gingivalis uses CD47 to hijack immune signaling pathways, effectively disabling the host’s ability to clear the infection. […] This mechanism helps explain why this bacterium thrives in inflammatory environments, leading to chronic periodontitis and potentially contributing to other systemic diseases. […] Using both in vitro and in vivo models, the researchers demonstrated that blocking CD47 or TSP-1 significantly enhanced bacterial clearance by the immune system. […] Mice lacking CD47 showed a higher ability to eliminate P. gingivalis, suggesting that targeting this pathway could provide a promising strategy for treating periodontal disease. […] „Current periodontal treatments focus on reducing bacterial load mechanically, but understanding how these bacteria evade immune responses opens new therapeutic possibilities,” Prof. Nussbaum added. […] „Targeting CD47-TLR2 signaling or TSP-1 could represent a novel approach to managing chronic infections linked to oral and systemic health.”
#53 Azthena logo with the word Azthena
https://www.news-medical.net/news/20250224/Study-uncovers-novel-immune-evasion-mechanism-used-by-key-bacterium-in-periodontitis.aspx
Our findings suggest that P. gingivalis uses CD47 to hijack immune signaling pathways, effectively disabling the host’s ability to clear the infection. […] This mechanism helps explain why this bacterium thrives in inflammatory environments, leading to chronic periodontitis and potentially contributing to other systemic diseases. […] Using both in vitro and in vivo models, the researchers demonstrated that blocking CD47 or TSP-1 significantly enhanced bacterial clearance by the immune system. […] Mice lacking CD47 showed a higher ability to eliminate P. gingivalis, suggesting that targeting this pathway could provide a promising strategy for treating periodontal disease. […] „Current periodontal treatments focus on reducing bacterial load mechanically, but understanding how these bacteria evade immune responses opens new therapeutic possibilities,” Prof. Nussbaum added. […] „Targeting CD47-TLR2 signaling or TSP-1 could represent a novel approach to managing chronic infections linked to oral and systemic health.”
#54
https://rsdjournal.org/index.php/rsd/article/view/48204
Introduction: Periodontal collapse will result in gingivitis and / or periodontitis. Inflammatory and immune reactions to the dental biofilm are its predominant findings. […] Understanding the mechanisms that govern the pathogenesis of periodontal diseases is a decisive factor in taking effective measures to control the disease. […] When bacterial components interact with the epithelium and are able to penetrate the connective tissue, an immune-inflammatory response of the host begins. If the microbial challenge remains unchanged, the inflammatory process will increase in the region. The conditions within the dental biofilm that is forming begin to favor the succession of bacterial species and lead to micro and macroscopic alterations of the periodontal tissues, which will be the result of the interaction between the microorganisms present in this biofilm and the tissues and inflammatory cells of the host.
#55
https://journals.lww.com/jisp/fulltext/2022/26030/models_of_periodontal_disease_pathogenesis__a.4.aspx
The revised model underscores the paradigm shift, from the primary role of bacteria in periodontal disease to bacterial colonization as a secondary event to inflammation. […] This model is based on the conceptual framework that periodontitis is a result of disruption of host-microbiome homeostasis. […] A healthy periodontal state is characterized by a symbiotic biofilm which triggers a proportionate and resolving host response. […] The evolution of the periodontal disease pathogenesis paradigm to a polymicrobial genetic dysbiosis model includes the polymicrobial synergy in a specific environment, the microbial dysbiotic gene expression, and the host genetic susceptibility to encompass the complexity of the periodontal diseases. […] The Page and Schroeder model proposed in 1976 provided a histopathologic roadmap to the pathologic events leading to clinical outcomes.
#56
https://rsdjournal.org/index.php/rsd/article/view/48204
The dental biofilm is fundamental to the beginning of the pathological process. It alone does not explain the variety of disease stages. So questions about the individual’s immune susceptibility may be the complementation of the response. Thus, the planning of periodontal treatment should be based on the scientific basis.
#57 Periodontal Disease (Gum Disease): Causes, Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/21482-gum-periodontal-disease
Gum disease isnt curable, but its manageable with appropriate treatment. You cant cure it because once you lose structural support around your teeth, you dont usually get all of it back. However, periodontal treatment can reduce infection and rebuild your bone and tissue to some degree. […] One stage of gum disease is totally reversible gingivitis (very early periodontal disease). If you detect gingivitis early enough, you can reverse it with regular dental cleaning and diligent oral hygiene. […] During this procedure, a periodontist places an artificial membrane between your gums and the newly placed bone grafting material. Soft tissue regenerates faster than bone, so the membrane keeps that space open so new bone can grow there instead of soft tissue.