Tendon Functional Extracellular Matrix

Screen, Hazel R. C.; Berk, David E; Kadler, Karl E.; Ramirez, Francesco; Young, Marian F.

doi:10.1002/jor.22818

Cited by 204 publications

(180 citation statements)

References 79 publications

(143 reference statements)

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“…Cross-linked collagen molecules assembled into collagen fibrils make up the minimal structural/functional mechanical unit of the tendon core. The core consists of densely packed type-I collagen matrix and the fibroblastic cells that maintain it [17,55]. The tendon core is wrapped with endotenon (the lowest level extrinsic compartment) to form fascicles, i.e.…”

Section: The Tendon Proper Its Composition and Structurementioning

confidence: 99%

“…Within a healthy tendon core, tenocytes attach to a highly ordered fibrillar collagen matrix (ECM) (Fig. 2) that is primarily composed of type-I collagen (65-80% of its dry mass), and small leucine-rich proteoglycans that regulate collagen self-assembly into collagen fibrils, which in turn are ordered by the cell into collagen fibers [17,55]. The structural terminology distinction is important -as fibrils are the basic subcellular collagen building blocks, whereas fibers are the relevant cell-scale structural units with which cells physically interact.…”

Section: Tendon Core -Multiscale Structure and Functionmentioning

confidence: 99%

“…This tissue barrier represents the first interface of ''handshaking" between the intrinsic and extrinsic tendon compartments. Higher level structural organization of tendon tissue reflects the function of the muscle-tendon unit, with fascicle-fascicle kinematics (sliding and stretching) that dictate the mechanical behavior of the tendon [12,17,[55][56][57][58][59][60]. The fibrillar collagen matrix also includes collagen III in various quantities.…”

Section: Tendon Core -Multiscale Structure and Functionmentioning

confidence: 99%

See 2 more Smart Citations

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

2017

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Section: The Tendon Proper Its Composition and Structurementioning

confidence: 99%

Section: Tendon Core -Multiscale Structure and Functionmentioning

confidence: 99%

Section: Tendon Core -Multiscale Structure and Functionmentioning

confidence: 99%

See 1 more Smart Citation

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

2017

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“…We set out to characterize the specific influences of the highly abundant collagenases on fibroblast-ECM crosstalk. In this study we used natural collagen fascicles (termed "ECM") from tendons of 6-mo-old rats (22,23). We examined the effect of this ECM on rat-1 fibroblasts, which are known to be sensitive to ECM composition and rigidity.…”

mentioning

confidence: 99%

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Solomonov

Zehorai

Talmi-Frank

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissueremodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition. We revealed striking differences in the motility and signaling patterns, morphology, and gene-expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, in contrast to previous notions, matrix-remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. Because ECM proteolysis is an abundant biochemical process that is critical for tissue homoeostasis, these results improve our fundamental understanding its complexity and its impact on cell behavior.T he function and integrity of the extracellular matrix (ECM) is vital for cell behavior as well as for whole-tissue homeostasis (1-4). The ECM undergoes constant remodeling during health and disease states. Its components are regularly being deposited, degraded, or otherwise modified. The highly stable fibrillar collagen type I (Col I) is abundant in many organ-derived ECMs and connective tissues (5, 6); it serves as a tissue scaffold, determining ECM mechanical properties and anchoring other ECM proteins necessary for cell function (7). These processes are orchestrated by multiple remodeling enzymes, among which the matrix metalloproteinase (MMP) family plays an important role. Only a few members of this proteinase family, the collagenases, are able to degrade the resistant fibrillar collagens, i.e., Col I, as well as other ECM molecules (8, 9). The collagenases have conserved amino acids in their zinc-containing catalytic domain (8, 10) and display high structural similarities, as reflected by their functional domain organization. Nevertheless, the complex effects exerted by different MMPs on ECM and cells in vivo remain poorly understood.The enzymatic activity of MMPs, and specifically of collagenases, in vivo is tightly regulated (11), with enzymatic dysregulation causing irreversible damage associated with a variety of diseases. Abnormally elevated levels of MMP-1 or of both MMP-1 and MMP-13 have been associated with different types of cancers and with inflammatory diseases (12-21).Here, we explored the degradation patterns of natural collagenrich ECM by two homologous MMPs and tested the response of cells to intact vs. selectively degraded ECM. We collectively profiled the unique remodeling events caused by two secreted collagenases, MMP-1 and MMP-13, by using biochemical, biophysical, and proteomics tools. We show that these proteases drive morphological, biochemical, and visc...

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“…4 While little is known about its exact function, elastin tends to be localized to the interfascicular matrix and likely contributes to sliding between adjacent tendon fascicles and recoil after mechanical loading. 21 Finally, intermixed with the collagen and non-collagen proteins of the tendon ECM is the gelatinous ground substance composed of proteoglycans (PGs) and glycosaminoglycans (GAGs). PGs and GAGs have a fixed net negative charge that allows them to retain water, which in turn helps the tendon to dissipate heat into the surrounding tissues as well as resist high compressive and tensile forces during exercise.…”

mentioning

confidence: 99%

Pathogenesis and management of tendinopathies in sports medicine

et al. 2018

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Tendinopathy is a major clinical problem in sports medicine and is often difficult to treat. Traditional therapeutic approaches have focused on reducing inflammation, yet research suggests that little to no inflammation is present in the tendons that fail to heal. The purpose of this review was to evaluate the effectiveness of the available treatment options for tendinopathy and to inform best clinical practices. A comprehensive search of electronic databases (PubMed, Google Scholar, and Web of Science) was conducted to identify relevant studies through June 2016. Studies were deemed relevant if they were published in English and contained original research on the management of tendinopathy in humans. Studies varied in methodological quality and were often limited by small sample size and lack of sufficient control groups. Critical evaluation of the literature suggests that physical therapy with or without eccentric exercise should be considered a first-line treatment. Corticosteroids and non-steroidal anti-inflammatory drugs provide short-term symptomatic relief, but long-term efficacy has not been demonstrated. Inconsistent results do not support the routine use of prolotherapy, platelet-rich plasma injections, and topical nitric oxide patches. Operative intervention should be reserved until conservative measures fail or an obvious operative lesion is present. While numerous therapeutic modalities exist for tendinopathy in the athlete, the ideal treatment protocol has not been clearly defined. The development of new targeted therapies for tendinopathy is likely to follow a greater understanding of the cellular and molecular mechanisms that underlie its pathogenesis.

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Tendon Functional Extracellular Matrix

Cited by 204 publications

References 79 publications

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Pathogenesis and management of tendinopathies in sports medicine

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