Review: Emerging concepts in the pathogenesis of tendinopathy

Dean, Benjamin; Dakin, Stephanie G.; Millar, Neal L.; Carr, Andrew

doi:10.1016/j.surge.2017.05.005

Cited by 79 publications

(111 citation statements)

References 73 publications

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“…The effects of T2DM on tendon homeostasis in the absence of acute injury have been largely overlooked in the basic science and pre‐clinical literature, which may be attributed to an insufficient appreciation for the magnitude of the clinical problem. However, chronic pathological changes to tendon structure represent a major clinical and social burden as patients experience decreased mobility and quality of life . Importantly, Zakaria et al found that T2DM patients were at a significantly greater risk of a tendon rupture requiring hospitalization, than non‐diabetics.…”

Section: Clinical Burdens Manifestations and Complications Of T2dm Omentioning

confidence: 99%

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Nichols

Loiselle

2019

Journal Orthopaedic Research

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Over 300,000 tendon repairs are performed annually in the United States to repair damage to tendons as a result of either acute trauma or chronic tendinopathy. Individuals with type II diabetes mellitus (T2DM) are four times more likely to experience tendinopathy, and up to five times more likely to experience a tendon tear or rupture than non‐diabetics. As nearly 10% of the US population is diabetic, with an additional 33% pre‐diabetic, this is a particularly problematic health care challenge. Tendon healing in general is challenging and often unsatisfactory due to the formation of mechanically inferior scar‐tissue rather than regeneration of native tendon structure. In T2DM tendons, there is evidence of an amplified scar tissue response, which may be associated with the increased the risk of rupture or impaired restoration of range of motion. Despite the dramatic effect of T2DM on tendon function and outcomes following injury, there are few therapies available to promote improved healing in these patients. Several recent studies have enhanced our understanding of the pro‐inflammatory environment of T2DM healing and have assessed potential treatment approaches to mitigate pathological progression in pre‐clinical models of diabetic tendinopathy. This review discusses the current state of knowledge of diabetic tendon healing from molecular to mechanical disruptions and identifies promising approaches and critical knowledge gaps as the field moves toward identification of novel therapeutic strategies to maintain or restore tendon function in diabetic patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:13–22, 2020

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Section: Clinical Burdens Manifestations and Complications Of T2dm Omentioning

confidence: 99%

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Nichols

Loiselle

2019

Journal Orthopaedic Research

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confidence: 99%

“…Interleukin‐1β (IL‐1β) is a crucial pro‐inflammatory mediator, secreted by immune cells and cells of some connective tissues at the inflammation site with a pivotal role in both homeostatic and pathological mechanisms. Increased levels of IL‐1β have been detected in tendons after prolonged mechanical loading (overuse), a known risk factor for tendinopathy . The exogenous supplementation of IL‐1β increases the expression of IL‐6, COX‐2, and MMPs in tendon cells and reduces the expression of tendon‐associated genes such as scleraxis and tenomodulin and collagen 1 and 3 in injured tendon‐derived progenitor cells (TPCs) .…”

mentioning

confidence: 99%

Pulsed Electromagnetic Field Modulates Tendon Cells Response in IL‐1β‐Conditioned Environment

Vinhas

Rodrigues

Gonçalves

et al. 2019

Journal Orthopaedic Research

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Strategies aiming at controlling and modulating inflammatory cues may offer therapeutic solutions for improving tendon regeneration. This study aims to investigate the modulatory effect of pulsed electromagnetic field (PEMF) on the inflammatory profile of human tendon‐derived cells (hTDCs) after supplementation with interleukin‐1β (IL‐1β). IL‐1β was used to artificially induce inflammatory cues associated with injured tendon environments. The PEMF effect was investigated varying the frequency (5 or 17 Hz), intensity (1.5, 4, or 5 mT), and duty‐cycle (10% or 50%) parameters to which IL‐1β‐treated hTDCs were exposed to. A PEMF actuation with 4 mT, 5 Hz and a 50% duty cycle decreased the production of IL‐6 and tumor necrosis factor‐α (TNF‐α), as well as the expression of TNFα, IL‐6, IL‐8, COX‐2, MMP‐1, MMP‐2, and MMP‐3, while IL‐4, IL‐10, and TIMP‐1 expression increased. These results suggest that PEMF stimulation can modulate hTDCs response in an inflammatory environment holding therapeutic potential for tendon regenerative strategies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:160–172, 2020

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“…Historically, there has been substantial debate about the terminology and if inflammation is of importance in the development and progression of tendinopathies (Khan et al, 2002; Khan et al, 2000). In contrast, more recent studies elegantly highlight the involvement of immune cells and activation of inflammatory processes in tendinopathy (Dean et al, 2017). However, the origin of these cells remains unknown and it is unclear if they mainly extravasate into the tissue upon injury or metabolic stress or if tendon-resident macrophages or mast cells exist in healthy tendon tissue initiating the first line response.…”

Section: Discussionmentioning

confidence: 99%

CX3CL1 and CX3CR1 Expressing Tendon Cells – A novel Immune Cell Population in the Tendon Core

Lehner

Spitzer

Gehwolf

et al. 2019

Preprint

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Tendon disorders frequently occur and recent evidence has clearly implicated the presence of immune cells and inflammatory events during early tendinopathy. However, the origin and properties of these cells remain poorly defined. Therefore, the aim of this study was to determine the presence of myleoid cells in healthy rodent and human tendon tissue and to characterize them. Using various transgenic reporter mouse models, we demonstrate the presence of tendon cells in the dense matrix of the tendon core expressing the fractalkine (Fkn) receptor CX3CR1 and its cognate ligand CX3CL1/Fkn. Pro-inflammatory stimulation of 3D tendon-like constructsin vitroresulted in a significant increase in the expression of IL-1β, IL-6, Mmp3, Mmp9, Cx3cl1, and epiregulin which has been reported to contribute to inflammation, wound healing, and tissue repair. Furthermore, we demonstrate that inhibition of the fractalkine receptor blocked tendon cell migrationin vitroand show the presence of CX3CR1/CX3CL1/EREG expressing cells in healthy human tendons. Taken together, we demonstrate the presence of CX3CL1+/CX3CR1+ “tenophages” within the healthy tendon proper potentially fulfilling surveillance functions in tendons.Summary StatementHere, we demonstrate the presence of a macrophage-like, CX3CL1/CX3CR1-expressing cell population within the healthy tendon proper potentially fulfilling a surveillance function.

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Review: Emerging concepts in the pathogenesis of tendinopathy

Cited by 79 publications

References 73 publications

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Pulsed Electromagnetic Field Modulates Tendon Cells Response in IL‐1β‐Conditioned Environment

CX3CL1 and CX3CR1 Expressing Tendon Cells – A novel Immune Cell Population in the Tendon Core

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