Molecular Events in Tendinopathy: A Role for Metalloproteases

Magra, Merzesh; Maffulli, Nicola

doi:10.1016/j.fcl.2005.01.012

Cited by 40 publications

(27 citation statements)

References 63 publications

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“…The failure to properly regulate downstream molecules leads to improper or excessive matrix degeneration and ultimately tendon dysfunction (Asundi and Rempel 2008). Among MMPs, MMP-2 is reported to modulate ECM remodeling in tendinopathy (De Mello Malheiro et al 2009;Skittone et al 2008;Magra and MuVulli 2005). The mechanism for the regulation of MMP-2 gene expression remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat

et al. 2010

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Both myofibroblast differentiation and extracellular matrix (ECM) deposition are essential components of scar formation in tendons, and hepatocyte growth factor (HGF) is reported to prevent fibrogenic responses in tendons. Matrix metalloproteinases-2(MMP-2) is also involved in the healing process in tendons. Whether HGF protects healed Achilles tendons from injury-induced scar formation and the mechanisms are unknown. Daily for 2 weeks after wounding, except for the non-surgical control group, the Achilles tendons in rats were locally injected with HGF (100 ng 50 μl(-1) per mouse) or phosphate-buffered saline (PBS). Histological examination showed HGF ameliorated disorganized collagen fibers caused by surgical incisions in rats. After transforming growth factor beta-1 (TGF-β1) induced fibrogenic responses in primary Achilles tendon fibroblasts in rats, HGF treatment for 24 h reduced α-smooth muscle actin (α-SMA) (0.60 ± 0.07-fold, P < 0.05) and type III collagen expression (0.39 ± 0.07-fold, P < 0.05). Moreover, HGF elevated MMP-2 expression (1.23 ± 0.11-fold, P < 0.05). The MMP-2 inhibitor, tissue inhibitors of metalloproteinase-1 (TIMP-1), partially blocked the inhibitory effects of HGF on α-SMA expression (from 0.60 ± 0.07-fold to 0.83 ± 0.07-fold, P < 0.05) and type III collagen expression (from 0.39 ± 0.06-fold to 0.86 ± 0.08-fold, P < 0.05). These results indicate HGF attenuates TGF-β1-induced fibrogenic responses in Achilles tendon, which was mediated by MMP-2. These results will aid in developing effective therapeutic approaches for the dysfunctional repair in Achilles tendons.

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Section: Discussionmentioning

confidence: 99%

HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat

et al. 2010

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“…The ECM in the main body of the tendon consists primarily of Type I collagen, while the predominant proteoglycan component is the small leucine-rich proteoglycan decorin, and the principal large aggregating proteoglycan is versican [17,18,19]. MMPs are involved in the remodeling of ECM through their broad proteolytic capability [22].…”

Section: Discussionmentioning

confidence: 99%

“…Tenocytes lie in the ECM and contribute to its homeostasis. Matrix metalloproteases (MMPs) are involved in remodeling of the extracellular matrix of tendons, and the various MMPs can be up-or down-regulated in tendinopathy [17]. A balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs) is required to maintain ECM homeostasis [24].…”

Section: Introductionmentioning

confidence: 99%

Collagens, Proteoglycans, MMP-2, MMP-9 and TIMPs in Human Achilles Tendon Rupture

Karousou

Ronga

Vigetti

et al. 2008

Clinical Orthopaedics &Amp; Related Research

Self Cite

152

114

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Tendon integrity depends on the extracellular matrix (ECM) metabolism which is regulated by proteolytic enzymes. However, it is unclear which enzymes play a role in tendon rupture. We studied the ECM of 19 ruptured human Achilles tendons, comparing the composition of specimens harvested close to the rupture with specimens harvested from an apparently healthy area in the same tendon. We compared gene expression of collagen Type I, decorin, and versican including enzymes involved in their metabolism as matrix metalloproteases (MMP-2 and -9) and tissue inhibitory of metalloproteinase (TIMP-1 and -2) using real-time PCR, zymography and FACE analysis. We found greater gene expression of proteoglycan core protein decorin and versican, collagen Type I, MMPs and TIMPs in the tendon rupture. Zymography analysis, reflecting expression of enzymatic activity, confirmed the gene expression data at protein level. Carbohydrate content was greater in the macroscopically healthy area than in the ruptured area. In the ruptured area, we found increased core protein synthesis but without the normal glycosaminoglycan production. The tissue in the area of rupture undergoes marked rearrangement at molecular levels and supports the role of MMPs in the pathology.

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“…It is known that in addition to changes in collagen production, both MMPs, which break down various types of collagen, and TIMPs, which regulate MMPs by inhibiting their activity, have been shown to be upregulated as well following exercise. [22][23][24] Thus, tendon matrix remodeling likely occurs in vivo as a result of TSC response to mouse treadmill running exercise; this may be one of the mechanisms responsible for tendon strengthening as Achilles tendon cells (ATCs). For both tendon cell cultures, including both TSCs and tenocytes, the treadmill running group produced a significantly higher level of collagen than the cage control group.…”

Section: Discussionmentioning

confidence: 99%

Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC‐related cellular production of collagen

Zhang

Pan

Liu

et al. 2010

Journal Orthopaedic Research

121

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Exercise is known to enhance tendon size and strength, but the stem cell-based mechanisms for such exercise-induced effects are largely unknown. This study aims to explore these mechanisms by using a mouse treadmill running model to examine the effects of exercise on newly discovered tendon stem cells (TSCs). After treadmill running, patellar TSCs (PTSCs) and Achilles TSCs (ATSCs) were isolated from the mice, and their proliferation was measured in vitro. We found that treadmill running nearly doubled proliferation rates of both PTSCs and ATSCs compared to cage control mice. Moreover, using a mixed tendon cell culture consisting of TSCs and tenocytes, cellular production of collagen was found to increase by 70% and 200% in PTSCs and ATSCs, respectively, from the treadmill running group over cells from the cage control group. These findings suggest that exercise exerts its anabolic effects on tendons at least in part by increasing proliferation to expand the pool of TSCs and also by increasing TSC-related cellular production of collagen, the predominant component of tendons. ß

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Molecular Events in Tendinopathy: A Role for Metalloproteases

Cited by 40 publications

References 63 publications

HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat

HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat

Collagens, Proteoglycans, MMP-2, MMP-9 and TIMPs in Human Achilles Tendon Rupture

Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC‐related cellular production of collagen

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