Materiały źródłowe

• #1 Pathogenesis of tendinopathies: inflammation or degeneration?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2714139/

  The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. […] It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. […] As will be clear in this review, we favor the hypothesis that inflammation and degenerative changes often coexist in the course of tendon disorders, and their relative contributions are difficult to dissect. […] Inflammatory and degenerative changes are not found in isolation in histopathological assessments of TP, and very often coexist in adjacent areas of pathological samples. […] The clinical relevance of these intratendinous degenerative changes is largely unknown: hypoxic degenerative TP, mucoid degeneration, tendolipomatosis, and calcifying TP, either alone or in combination, can be seen in a high percentage of the urban population of healthy, asymptomatic individuals who are at least 35 years old.

• #2 Review: Emerging concepts in the pathogenesis of tendinopathy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714045/

  Tendinopathy is a common clinical problem and has a significant disease burden attached, not only in terms of health care costs, but also for patients directly in terms of time off work and impact upon quality of life. […] Controversy surrounds the pathogenesis of tendinopathy, however the recent systematic analysis of the evidence has demonstrated that many of the claims of an absence of inflammation in tendinopathy were more based around belief than robust scientific data. […] The pathogenesis of tendinopathy is certainly multifactorial and complex. […] Increased age is a key risk factor for the development of tendinopathy, […] although the commonly affected tendons all experience high levels of mechanical stress and over-use is a frequently implicated risk factor. […] Recent systematic reviews have clearly demonstrated that patients with high cholesterol and diabetes are at significantly higher risk of developing tendinopathy,

• #3 Tendonitis: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/809692-overview

  Tendons transmit the forces of muscle to the skeleton. As such, they are subjected to repeated mechanical loads, which are felt to be a major causative factor in the development of tendinopathy. Pathologic findings include tendon inflammation, mucoid degeneration, and fibrinoid necrosis in tendons. Microtearing and proliferation of fibroblasts have also been reported. However, the exact pathogenesis of tendinopathy is unclear. […] The term tendinosis refers to the histopathologic finding of tendon degeneration. The term tendinopathy is a generic term used to describe a common clinical condition that affects the tendons, causing pain, swelling, or impaired performance. Because of the fact that most pain from tendon conditions is not actually inflammatory in nature, tendinopathy may be a better term than tendonitis.

• #4 Review: Emerging concepts in the pathogenesis of tendinopathy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714045/

  Several studies have stated that no inflammatory cells were present in samples from tendinopathic patients but had only looked for neutrophils, not other types of inflammatory cell. […] In fact the evidence to support the role of inflammation in tendinopathy pathogenesis has become increasingly overwhelming in recent years with a majority of studies demonstrating increased numbers of macrophages in diseased tendons. […] Macrophages are known to play an essential role orchestrating inflammation and tissue repair. […] Increasing evidence has shown that inflammatory mechanisms and the innate immune system are activated within the tendon matrix microenvironment during tissue injury and dysregulated homeostasis. […] Thus while the functional contribution of cytokine biology and its downstream consequences in tendinopathy remains to be established there is now a convincing scientific rationale towards translational immunobiology to benefit tendinopathy patients. […] Fundamentally a better understanding of the pathogenesis of tendinopathy and the underlying mechanisms is essential if we are to develop more effective long term treatment strategies for the management of tendinopathy.

• #5 Revisiting the continuum model of tendon pathology: what is its merit in clinical practice and research? | British Journal of Sports Medicine

  https://bjsm.bmj.com/content/50/19/1187

  The pathogenesis of tendinopathy and the primary biological change in the tendon that precipitates pathology have generated several pathoaetiological models in the literature. […] The continuum model proposed a model for staging tendinopathy based on the changes and distribution of disorganisation within the tendon. However, classifying tendinopathy based on structure in what is primarily a pain condition has been challenged. […] The interplay between structure, pain and function is not yet fully understood, which has partly contributed to the complex clinical picture of tendinopathy. […] The continuum model is one of several models on the pathoaetiology of tendon pathology. These tendon pathology models can be divided into three groups depending on the primary or key event in the pathology cascade: (1) collagen disruption/tearing, (2) inflammation or (3) tendon cell response.

• #6 Spectrum of Tendon Pathologies: Triggers, Trails and End-State

  https://www.mdpi.com/1422-0067/21/3/844

  Curative and tailored management relies not only on full understanding of the tendon pathogenesis but also on appropriate, widely accepted and guiding classification and staging systems, which would be beneficial for rational and adequate patient-targeted therapy. […] Based on clinical and basic scientific studies in humans, Cook and Purdam (2009) established the continuum theory for pathogenesis of tendinopathy from asymptomatic tendons to tendon injuries claiming that tendon pathogenesis is a continuum, not an absolute. […] These phases are 1) early reactive tendinopathy (non-inflammatory proliferative response in cells and matrix) in response to acute overload or trauma, 2) failed healing response and disrepair of the ECM and finally, 3) terminal degeneration and dysregulation of healing resulting in irreversible stage of pathology showing major structural and compositional changes, cell death, tissue breakdown and loss of function with predisposition of the tendon to further injury and rupture.

• #7 Revisiting the continuum model of tendon pathology: what is its merit in clinical practice and research? | British Journal of Sports Medicine

  https://bjsm.bmj.com/content/50/19/1187

  The normal tendon tissue responds to load with both synthesis and degradation of the matrix; however, turnover rates vary depending on the protein. […] We proposed that reactive pathology results in an increase in large proteoglycans but further consideration and recent studies suggest that there must be an earlier phase that is less intense and potentially transient. […] The continuum model suggested that management may be optimised by tailoring interventions to the stage of pathology and targeting the primary driver (cell activation) and inter-related alterations in matrix integrity. […] Tendinopathy is a heterogeneous clinical presentation due to the variable change in matrix structure, pain and dysfunction. […] The continuum model provided a framework to understand the potential of the tendon to regain normal structure.

• #8 Revisiting the continuum model of tendon pathology: what is its merit in clinical practice and research? | British Journal of Sports Medicine

  https://bjsm.bmj.com/content/50/19/1187

  In degenerative tendinopathy, interventions influencing tendon structure are less critical, as the pathology appears to have limited reversibility. […] The pathological tendon appears to effectively compensate for areas of disorganisation by increasing in cross-sectional dimension to maintain sufficient volumes of aligned fibrillar structure. […] The addition of additional cells (stem or tenocytes) into a hypercellular environment would appear counter-intuitive, as the ability to recreate a viable cell-matrix relationship is limited in a frankly degenerative region of the tendon that is unable to transmit tension. […] It is unlikely that any one model fully explains all aspects of the pathoaetiology of tendon pathology and its links to pain and function, as these processes and relationships are complex.

• #9 Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-019-0364-x

  Mechanical loading is an important factor in musculoskeletal health and disease. […] Pathological levels of force represent a biological (mechanical) stress that elicits an immune system-mediated tissue repair pathway in tendons and ligaments. […] The role of mechanical stress in overuse injuries, such as tendinopathy, has long been known, but mechanical stress is now also emerging as a possible trigger for some forms of chronic inflammatory arthritis, including spondyloarthritis and rheumatoid arthritis. […] Thus, seemingly diverse diseases of the musculoskeletal system might have similar mechanisms of immunopathogenesis owing to conserved responses to mechanical stress. […] Mechanical loading is a well-defined factor in the immunopathology of tendon and ligament disorders such as tendinopathy.

• #10 Review: Emerging concepts in the pathogenesis of tendinopathy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714045/

  Recent evidence has shown that tendon overload is linked to alterations in cell shape, as well as increased markers of inflammation and matrix degradation. […] It may be therefore be postulated that interactions between the tendon, the interfascicular matrix and adjacent fat pads are instrumental in the development of tendinopathy, with the latter being a key potential source of key cytokines and inflammatory cells. […] This may help explain the presence of persistent inflammation in tendinopathy, […] a phenomenon which has been shown to have important effects on tendon cells in vitro. […] The neuronal response to tendon injury involves nerve in growth during the initial inflammatory phase; the subsequent proliferative and remodelling phases are regulated by sensory nerves, as well as the glutaminergic and autonomic systems.

• #11

  https://journals.lww.com/nrronline/fulltext/2022/10000/novel_insights_into_the_pathogenesis_of_tendon.27.aspx

  Tendon pathology is characterized by damage to the tendon structural integrity with disruption of collagen fibers (Nourissat et al., 2015). […] In chronic conditions (or tendinopathy), symptoms include changes in both locomotor and sensorial functions of the tendon (Nourissat et al., 2015; Scott et al., 2020). […] The molecular and neural mechanisms controlling proliferation, migration, and differentiation of TSCs as well as pain and locomotor impairment are not well understood, but new insights have shown the relevant but yet ignored role of mechanotransduction and neuroplasticity. […] Mechanical forces are perceived by tenocytes and TSCs as stimuli through diverse intermediaries and converted to biochemical signals, finally promoting a cellular response. […] Change in tension perceived by cells in a specific location can be transmitted to cells in other regions through signaling via connexins, integrins, G protein-coupled receptors, and growth factor receptor (Wang et al., 2020).

• #12 Exercise and Tendon Remodeling Mechanism | IntechOpen

  https://www.intechopen.com/chapters/66124

  Tendons connect muscles to bones and transmit the force exerted by the corresponding muscle to the skeleton and, therefore, are key components for locomotion. They are responsive to mechanical factors, which are essential for cellular functioning, tendon development, homeostasis, and repairing. Mechanical signals are transduced via molecular signaling pathways which trigger tendon adaptive responses. […] A possible mechanism that explains the structural changes noticed following mechanical loading is the tendon responsiveness to mechanotransduction, promoting the interaction between fibroblasts and ECM. It is believed that this interaction between fibroblasts and ECM permits the cells to sense and respond to mechanical stimuli, promoting intracellular signaling that will improve protein synthesis and, consequently, tendon structures through collagen and growth factor autocrine/paracrine release.

• #13 Management of Chronic Tendon Injuries | AAFP

  https://www.aafp.org/pubs/afp/issues/2019/0801/p147.html

  Chronic tendon injuries are common athletic and occupational injuries that account for many physician visits. Tendons have a complex biology that provides a unique combination of strength, flexibility, and elasticity but also predisposes them to injury. The term tendinopathy is preferred to tendinitis because of the presence of a disordered and degenerative healing process not inflammation in the pathologic tendon. […] Although inflammation may be present, tendinopathy is primarily a degenerative process in which a failed healing response leads to pain and dysfunction. […] Tendons are biologically complex structures composed of multiple layers of tightly packed collagen fibers that are produced by tenocytes and tenoblasts. Tenocytes are mechano-receptive cells that are able to change their gene expression in response to demand. Tendons’ unique combination of strength, flexibility, and elasticity allows them to carry loads and maintain tensile strength for long periods of time. Because they have a lower rate of oxygen consumption than skeletal muscle, they are also slow to heal. Tendons receive their blood supply from a variety of sources, and pathology usually occurs in the hypovascular or watershed areas between two sources of blood supply. Appropriate loads on a tendon are anabolic, but overloading a tendon can be catabolic and catastrophic. Disrupting the homeostasis between tendon stress and repair damages the tendon.

• #14 Physical therapy in Guilford and Old Saybrook for Knee Pain – Patellar Tendonitis

  https://www.physicaltherapyspecialists.org/article.php?aid=1550

  Patellar tendonitis (also known as jumper’s knee) is a common overuse condition associated with running, repeated jumping and landing, and kicking. […] Patellar tendonitis occurs most often as a result of stresses placed on the supporting structures of the knee. […] Overuse is simply a mismatch between the load or stress on the tendon and the ability of that tendon to distribute the force. If the forces placed on the tendon are greater than the strength of the structure, then injury can occur. Repeated microtrauma at the muscle-tendon junction may overcome the tendon’s ability to heal itself. Tissue breakdown occurs, often triggering an inflammatory response that leads to tendonitis. […] Chronic tendonitis is really a problem called tendonosis. Inflammation is not present. Instead, degeneration and/or scarring of the tendon has developed. Chronic tendon injuries are much more common in older athletes (30 to 50 years old).

• #15 Surprising Causes of Tendonitis | Center for Orthopaedic Surgery & Sports Medicine

  https://www.centerfororthosurgery.com/surprising-causes-of-tendonitis/

  Pain, soreness, redness, swelling. These are all-too-common orthopaedic symptoms of tendonitis, a chronic inflammatory condition seen by your sports medicine doctor in San Antonio. […] When you overuse or injure a tendon, you experience pain, swelling, and limited motion in the affected body part. […] There are many causes for tendonitis, the most common of which is overuse. People typically develop this condition when exercising, playing a sport, or due to occupational duties and hobbies that require repetitive movements of the same nature. Another common cause is aging. The older you get, the more likely you are of developing tendonitis. […] The high blood glucose levels characteristic of diabetes commonly lead to frozen shoulder or rotator cuff tendonitis. While physicians and researchers cannot pinpoint the exact mechanism for its development, tendonitis and other inflammatory conditions, such as arthritis, are fairly common among diabetics.

• #16 Physical therapy in Linwood for Knee Pain – Quadriceps Tendonitis

  https://www.parkinsonlifecenterofsouthernnj.org/Injuries-Conditions/Knee/Knee-Issues/Quadriceps-Tendonitis-of-the-Knee/a~1803/article.html

  Alignment or overuse problems of the knee structures can lead to strain, irritation, and/or injury of the quadriceps muscle and tendon. This produces pain, weakness, and swelling of the knee joint. […] Quadriceps tendonitis occurs most often as a result of stresses placed on the supporting structures of the knee. Running, jumping, and quick starts and stops contribute to this condition. Overuse injuries from sports activities is the most common cause but anyone can be affected, even those who do not participate in sports or recreational activities. […] Strength of the patellar tendon is in direct proportion to the number, size, and orientation of the collagen fibers that make up the tendon. Overuse is simply a mismatch between load or stress on the tendon and the ability of that tendon to distribute the force. If the forces placed on the tendon are greater than the strength of the structure, then injury can occur. Repeated microtrauma at the muscle tendon junction may overcome the tendon’s ability to heal itself. Tissue breakdown occurs triggering an inflammatory response that leads to tendonitis and even partial tears. Chronic quadriceps tendonitis is really a problem called tendonosis. Inflammation is not present. Instead, degeneration and/or scarring of the tendon has developed. Chronic tendon injuries are much more common in older athletes (30 to 50 years old).

• #17 Physiotherapy in Coaldale for Knee Pain – Quadriceps Tendonitis

  https://www.impacthealthcoaldale.ca/article.php?aid=1803

  Quadriceps tendonitis occurs most often as a result of stresses placed on the supporting structures of the knee. […] Overuse is simply a mismatch between load or stress on the tendon and the ability of that tendon to distribute the force. […] Repeated microtrauma at the muscle tendon junction may overcome the tendon’s ability to heal itself. […] Tissue breakdown occurs triggering an inflammatory response that leads to tendonitis and even partial tears. […] Chronic quadriceps tendonitis is really a problem called tendonosis. Inflammation is not present. Instead, degeneration and/or scarring of the tendon has developed. […] The aim of our treatment is to calm pain and inflammation, to correct muscle imbalances, and to improve the function of the quadriceps mechanism.

• #18 Physical therapy in Wellesley for Knee Pain – Patellar Tendonitis

  https://www.advancedorthopedic.net/Injuries-Conditions/Knee/Knee-Issues/Patellar-Tendonitis/a~1550/article.html

  Patellar tendonitis occurs most often as a result of stresses placed on the supporting structures of the knee. […] Overuse is simply a mismatch between the load or stress on the tendon and the ability of that tendon to distribute the force. If the forces placed on the tendon are greater than the strength of the structure, then injury can occur. Repeated microtrauma at the muscle-tendon junction may overcome the tendon’s ability to heal itself. Tissue breakdown occurs, often triggering an inflammatory response that leads to tendonitis. […] Strength of the patellar tendon is in direct proportion to the number, size, and orientation of the collagen fibers that make up the tendon. […] Chronic tendonitis is really a problem called tendonosis. Inflammation is not present. Instead, degeneration and/or scarring of the tendon has developed. Chronic tendon injuries are much more common in older athletes (30 to 50 years old).

• #19 Pathogenesis of tendinopathies: inflammation or degeneration?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2714139/

  The transition to the symptomatic phase is usually marked by characteristic histological changes: the invasion of vessels is followed by nerve proliferation, and glutamate levels increase and are responsible for pain during the course of the disease. […] In conclusion, it is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenetic cascade of TPs.

• #20 Review: Emerging concepts in the pathogenesis of tendinopathy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714045/

  Glutamate has been shown to induce pain and hyperalgesia when injected around human tendon tissue. […] An upregulation of the glutaminergic signalling has been linked to inflammatory change in a rat supraspinatus model. […] This histological and immunohistochemical study demonstrated that an increase in glutamate staining was present in the painful tendinopathic rotator cuff tendons alongside the classical histological changes which included increased collagen disorganization and cellularity. […] This study has also shown significant staining of certain ionotropic and metabotropic receptors on tendon cells residing in damaged rotator cuff tissue, for example NMDAR1 and mGluR1. […] This study did not find any correlation with the severity of patient pain symptoms. […] The first study to recognize the presence of glutamate in tendinopathy used a microdialysis technique in chronic painful Achilles tendinopathy.

• #21 Tendon pain – what are the mechanisms behind it?

  https://www.degruyterbrill.com/document/doi/10.1515/sjpain-2022-0018/html?lang=en&srsltid=AfmBOooXlJP6m8thJHFy1ctNcqSc7puJeL6eaUnwKXcfFot0xbvO7E2I

  Current treatments that entail the highest scientific evidence to mitigate chronic tendon pain include eccentric exercises and extracorporeal shockwave, which both target peripheral neoinnervation aiming at nerve regeneration. […] Potential mechanism-based pharmacological treatment approaches could be developed by blocking promotors of nerve ingrowth, such as NGF, and promoting inhibitors of nerve ingrowth, like semaphorins, as well as blocking glutamate-NMDA-receptor pathways, which are prominent in chronic tendon pain. […] This topical review found no correlations between radiological and histological tissue alterations including neovascularization and chronic tendon pain. Substantial evidence, however, was found suggesting that chronic painful tendons exhibit (1) protracted ingrowth of sensory nerves (2) elevated pain mediator levels and (3) up-regulated expression and excitability of pain receptors, which participate in a (4) neuro-immune pathways involved in pain regulation.

• #21 Tendon pain – what are the mechanisms behind it?

  https://www.degruyterbrill.com/document/doi/10.1515/sjpain-2022-0018/html?lang=en&srsltid=AfmBOooXlJP6m8thJHFy1ctNcqSc7puJeL6eaUnwKXcfFot0xbvO7E2I

  Management of chronic tendon pain is difficult and controversial. This is due to poor knowledge of the underlying pathophysiology of chronic tendon pain, priorly known as tendinitis but now termed tendinopathy. The objective of this topical review was to synthesize evolving information of mechanisms in tendon pain, using a comprehensive search of the available literature on this topic. […] The synthesis demonstrated that chronic tendon pain, however, is characterized by excessive nerve sprouting with ingrowth in the tendon proper, which corresponds to alterations observed also in other connective tissues of chronic pain conditions. […] Chronic painful tendons exhibit elevated amounts of pain neuromediators, such as glutamate and substance P as well as up-regulated expression and excitability of pain receptors, such as the glutamate receptor NMDAR1 and the SP receptor NK1, found on ingrown nerves and immune cells.

• #22 Management of Chronic Tendon Injuries | AAFP

  https://www.aafp.org/pubs/afp/issues/2019/0801/p147.html

  The etiology of pain associated with chronic tendinopathy is unclear but has been attributed to neovascularization, neurochemicals, and mechanical breakdown. Patients typically present with localized pain of insidious onset that is often associated with beginning a new activity or increasing the intensity of regular activities. […] If prevention is not possible, early identification and treatment of an improper tendon response to loading activities will minimize the chance of progression to a chronic injury.

• #23 Review: Emerging concepts in the pathogenesis of tendinopathy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714045/

  The co-localisation of NMDAR1 and CD206 suggests that certain glutamate receptors are predominantly expressed on inflammatory type cells within tendon. […] Recent mechanistic dissection has highlighted a role for the cytokine IL-33, a member of the IL-1 cytokine family that plays a major role in innate and acquired immune responses, in matrix/inflammatory crosstalk in tendon damage. […] Taken together these studies demonstrate a key functional role for IL-33 in early injury induced matrix dysregulation and subsequent cytokine feedback mechanisms that have an ultimate biomechanical and clinical effect. […] The dwindling of popularity of the term tendinitis represented skepticism regarding the role of inflammation in tendon degeneration. […] Recent systematic analysis of the evidence has demonstrated that many of the claims of an absence of inflammation in tendinopathy were more based around belief than robust scientific data.

• #24 Tendon pain – what are the mechanisms behind it?

  https://www.degruyter.com/document/doi/10.1515/sjpain-2022-0018/html?lang=de

  Increasing evidence indicates that mast cells serve as an important link between the peripheral nervous system and the immune systems resulting in so-called neurogenic inflammation. […] Chronic painful tendons exhibit (1) protracted ingrowth of sensory nerves (2) elevated pain mediator levels and (3) up-regulated expression and excitability of pain receptors, participating in (4) neuro-immune pathways involved in pain regulation. […] Potential mechanism-based pharmacological treatment approaches could be developed by blocking promotors of nerve ingrowth, such as NGF, and promoting inhibitors of nerve ingrowth, like semaphorins, as well as blocking glutamate-NMDA-receptor pathways, which are prominent in chronic tendon pain.

• #25

  https://journals.lww.com/nrronline/fulltext/2022/10000/novel_insights_into_the_pathogenesis_of_tendon.27.aspx

  Thus, as in inflammation, mechanotransduction also has its own signaling, but we still need to understand how mechanical forces are converted to molecular, cellular, and functional processes. […] The growth of new nerves into the disorganized collagen mesh favors the consolidation of tissue architecture that is unfavorable to the original function of the tendon to receive and transmit high levels of tension, since sensory neuropeptides start to contribute permanently to the tissue dynamics a process called neurogenic inflammation (van Sterkenburg and van Dijk, 2011). […] Understanding the actual roles of glial cells in tendon injury is in progress, especially moved by their recent recognition as important regulators of neuronal functions, either for benefits or harms. […] The contribution of the nervous system to tendon modulation may help explain why, in the condition of tendinous denervation, there is a reduction in the load to failure for the injured tendon and histological changes compatible with tendinopathy in healthy denervated tendons (El-Habta et al., 2018). […] Finally, even though the inflammatory process resulting from tendon injury has a great clinical impact, the new evidence presented above indicate that mechanotransduction and neural plasticity are relevantly involved in tissue repair and should also be considered during patient management.

• #26 Activated Tendon Stromal Cells Drive a Type 17 Immune Response Via CCL20: A Potential Role in the Pathogenesis of Enthesitis in Psoriatic Arthritis – ACR Meeting Abstracts

  https://acrabstracts.org/abstract/activated-tendon-stromal-cells-drive-a-type-17-immune-response-via-ccl20-a-potential-role-in-the-pathogenesis-of-enthesitis-in-psoriatic-arthritis/

  Activated Tendon Stromal Cells Drive a Type 17 Immune Response Via CCL20: A Potential Role in the Pathogenesis of Enthesitis in Psoriatic Arthritis […] While the exact pathogenesis of psoriatic arthritis (PsA) remains unclear, it is recognised that several environmental factors operate in individuals with genetic susceptibility leading to sustained inflammatory responses. […] However, the mechanisms linking mechanical stress/damage at the enthesis/tendon which leads to immune cell activation remains unknown. […] In conclusion, our results support a role of the tendon stromal compartment in the development of a type 17 immune response in PsA.

• #27 Mechanism of osteogenic and adipogenic differentiation of tendon stem cells induced by sirtuin 1

  https://www.spandidos-publications.com/10.3892/mmr.2016.5417

  Sirt1 is a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, which has an important role in energy metabolism and cell differentiation. A study has shown that Sirt1 can regulate osteogenic differentiation by self-deacetylation in mesenchymal stem cells. Resveratrol, an activator of Sirt1, can decrease the number of adipocytes and increase the expression of osteoblast markers. Inhibition of Sirt1 can increase the number of adipocytes and lipoblast markers and reduce the expression of osteoblast markers. Thus, the activation of Sirt1 can inhibit adipogenic differentiation and promote osteogenic differentiation. However, the expression status of Sirt1 in TSCs and the underlying mechanisms of its possible regulation of osteogenic and adipogenic differentiation in TSCs have remained elusive.

• #28 Impaired function of tendon-derived stem cells in experimental diabetes mellitus rat tendons: implications for cellular mechanism of diabetic tendon disorder | Stem Cell Research & Therapy | Full Text

  https://stemcellres.biomedcentral.com/articles/10.1186/s13287-018-1108-6

  Patients with diabetes mellitus (DM) often suffered with many musculoskeletal disorders, such as tendon rupture and tendinopathy. However, the understanding of the pathogenesis of these alternations is limited. […] These results suggested the erroneous differentiation of dTDSCs might account for the structural and non-tenogenic alternations in DM tendons, which provided new cues for the pathogenesis of tendon disorders in DM. […] The underlying mechanism of the pathological changes in diabetic tendons still remained unclear. […] The micro-tears, red blood cells, and blood vessels were also discovered in DG tendons while the vessels could not be found in CG tendons. […] The increased number of vessels in tendons of both DM patients and animal models was also reported. […] Therefore, the increased angiogenesis and upregulated VEGF expression also indicated the formation of chronic tendinopathy in DM subjects.

• #29 Impaired function of tendon-derived stem cells in experimental diabetes mellitus rat tendons: implications for cellular mechanism of diabetic tendon disorder | Stem Cell Research & Therapy | Full Text

  https://stemcellres.biomedcentral.com/articles/10.1186/s13287-018-1108-6

  The dTDSCs which isolated from STZ-induced DM rats showed the significantly decreased proliferation capacity and colony-forming ability than the normal healthy TDSCs, and the erroneous differentiation of dTDSCs with higher osteo-chondrogenic and lower tenogenic differentiation abilities might contribute to the non-tenogenic alternations of tendons in STZ-induced DM rats, further impair its self-managing ability, and develop into histopathological characteristic alterations of diabetic tendon disorders.

• #30 What is the Pathogenesis of Tendon Degeneration? – Andarawis-Puri Research Group

  https://andarawispurilab.mae.cornell.edu/researchareas/pathogenesis-of-tendon-degeneration/

  We have shown that sub-rupture damage can accumulate from just one bout of fatigue loading. […] We have found that tendons ineffectively repair accumulated sub-rupture fatigue damage and therefore become increasingly predisposed to further injury. […] This induced sub-rupture damage does not innately remodel, and early onset of damage subjects the tendon to a sustained risk of accumulation of further injury. […] Higher levels of severity of the initial damage induced prompt an increasingly muted and ineffective biological response, which ultimately results in diminished repair. […] Our goal is to determine whether some of the observed changes are manifestations of the tendon damage, or part of an attempt (albeit ineffective without further perturbation) to repair. […] The role of inflammation in chronic tendinopathy has been a topic of great controversy. […] it is unclear whether inflammation plays any role in the pathogenesis or the attempted (albeit ineffective) repair response of tendinopathy.

• #31 A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy

  https://www.mdpi.com/1422-0067/25/3/1868

  A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy […] Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. […] We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. […] Tendinopathy affects more than 30 million people annually, impacting their health and quality of life, and it can even be career-ending for some athletes. […] The role of inflammation in tendinopathy is not clearly established and is still a matter of debate.

• #32 A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy

  https://www.mdpi.com/1422-0067/25/3/1868

  The presence of macrophages in an injured tendon has been reported to accelerate the healing process by increasing cell proliferation and ECM generation. […] Our analyses collectively demonstrated that our model follows the same degenerative processes observed in similar animal models and in human patients. […] The obtained histological data confirmed that our rat model of patellar tendinopathy showed signs of tissue disorganization, hypercellularity, and intra-tendinous calcifications at 60 days post-injury, as well as an increase in tendon size, as observed in other models established to reproduce this disease. […] The prompt and strong increase in α-SMA and CD31 vascular markers demonstrated the appearance of strong intra-tendinous neovascularization, which is also associated with the natural process of tendon repair.

• #33 Tendonitis Treatment | Rise Physical Therapy | NWA

  https://www.riseptnwa.com/what-is-tendonitis-tendinopathy/

  The final stage is the degenerative stage, also labeled the “clinical presentation,” as this is typically when patients seek medical attention. […] This is when tendons are most susceptible to ruptures, and also where we start to see large scale degenerative changes in both the extracellular matrix and within the tissue cells (which is what may lead to those ruptures). […] Tendonitis can often be effectively managed and even resolved with physical therapy alone, especially in mild to moderate cases. […] Physical therapy plays a significant role in promoting healing, reducing pain, and restoring normal function to the affected tendon and surrounding tissues.

• #34 Tendonitis (Tendinitis): Causes, Symptoms & Treatments | HSS

  https://www.hss.edu/condition-list_tendonitis.asp

  Tendonitis is most commonly caused by overuse (repetitive stress), but less often, it can also occur in areas where calcium deposits have developed. As people age, repetitive motion, such as from sports or work activities, can injure the tendon where it attaches to the bone, promoting an inflammatory response by the body. […] It is very important that you do not neglect persistent tendonitis, since recurring tendonitis can lead to degeneration of the tendon, known as tendinosis. In addition, you should consult a specialist in orthopedics or sports medicine to properly diagnose and treat your pain. Surgical intervention by an experienced orthopedist may be necessary to avoid ongoing unresponsive symptoms, particularly if your weakened tendon is at risk of tearing or rupture. […] In the most severe cases where nonsurgical treatments do not lead to good outcomes, surgery can realign tendons, remove bone spurs that may be causing pressure on tendons, and remove areas of calcium buildup. In some cases, persistent tendon inflammation combined with overuse especially of the Achilles tendon or shoulder rotator cuff tendons may lead to weakening and subsequent rupture of the tendon. Once a tendon has become irreversibly damaged or has ruptured, treatment options (and ultimate outcomes) are often very limited.

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