Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology

Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

“…The levels of MMP‐1 increased with loading, correlating with previous studies, which have shown increased MMP‐1 expression in tendinopathic44, 45 or ruptured46 tendons. Further, MMP‐1 expression has recently been shown to increase with overload fatigue inducing exercise in equine tendons 47.…”

Tendinopathy and statin use: The role of matrix metalloproteinases or eicosanoids? Comment on the letter by Beri and Khattri and the article by Marie et al

“…Although Marie et al (2) had previously reported that statin-associated tendon toxicity might be due to 1) reduced cholesterol content of tendon cell membranes, making them unstable, or 2) reduced levels of regulatory proteins involved in the maintenance of tendon cells, Beri and Khattri (1) described that hydroxymethylglutaryl-coenzyme A blockers acting as matrix metalloproteinase (MMP) inhibitors are quite attractive, because it was reported that simvastatin inhibited MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway (3). The possible role of MMPs in the statin-associated tendinopathy was first postulated by Pullatt et al (4), who speculated that the inhibition of MMP-9 and augmentation of tissue inhibitor of metalloproteinases 1 (TIMP-1) in macrophages by statins could impair tendon remodeling and contribute to tendinopathy.…”

“…First, the systemic effect of statins on serum MMP levels has been reported (5), but the changes of MMPs within tendons after statin use have not been previously reported in any study, including the study by Pullatt et al (4).…”

The role of proteases in pathologies of the synovial joint

“…A number of degenerative changes have been reported including, hypoxia, loss Drake et al (1996), Everts et al (1992), Garnero et al (1998), Hou et al (1999), Kamiya et al (1998) MMP-13 Metallo Cleavage of matrix from demineralised zones Delaissé et al (2003), Everts et al (2002), Fuller and Chambers (1995) Osteoclast activation and migration MMP-13 Metallo Cleavage of type I collagen generating an activation factor for osteoclasts Millar et al (1998), Riley et al (2002) of fibrillar collagen structure, glycosaminoglycan accumulation between the collagen fibres and cell rounding together with an absence of inflammatory cells (Kannus & Józsa, 1991). Similar changes have been reported in chronic tendinopathy, including an abnormal fibre structure and arrangement, focal changes in cellularity, rounded cells and an increase in proteoglycan content (Movin, Gad, Reinholt, & Rolf, 1997).…”

“…Analyses of the type III collagen content and of slow-forming collagen cross-links have indicated that collagen turnover is increased in chronic pathologies (Bank, TeKoppele, Oostingh, Hazleman, & Riley, 1999). MMP proteases have been implicated in this collagen turnover and comparisons of normal and ruptured tendon have demonstrated an increase in the amount of active MMP-1, and a decrease in the amounts of MMP-2 and -3 together with increased collagen denaturation and turnover (Riley, 2005;Riley et al, 2002). A key role for the inhibition of metalloprotease activity in the development of tendinopathy is inferred from the effects of the broad-spectrum metalloprotease inhibitor Marimastat, which induces tendinopathy by an unknown mechanism (Millar et al, 1998).…”