Gene Expression of Matrix-Degrading Enzymes in Patellar Tendinopathy

Abstract

Introduction A predominant feature of tendinopathy is a change in the appearance and organisation of the extracellular matrix including greater amounts of the large aggregating proteoglycans, aggrecan and versican. We have shown that in patellar tendinopathy these large proteoglycans are also rapidly degraded so that mainly fragments remain in the tissue. 1 This catabolism of large proteoglycans is likely to be mediated by a number of matrix-degrading proteinases such as the matrix metalloproteinases (MMPs) and the aggrecanases (ADAMTSs).The aim of this work was to investigate whether in patellar tendinopathy there is a change in the gene expression of the matrix proteinases involved in proteoglycan catabolism including the MMPs and ADAMTSs, as well as their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). Methods Total mRNA isolated from ∼100mg tissue samples of normal (n=9) and pathologic (n=12) tendon was assayed by relative quantitative RT-PCR for MMP (-1, -2, -3, -9, and -13), ADAMTS (-1, -4, -5), and TIMP (-1, -2, -3, and -4), and normalised to GAPDH. Results Expression of mRNA for MMP-9 and TIMP-1 was significantly up-regulated in pathologic tendons ( p=0.019 and p=0.013, respectively). A trend toward a down-regulation of expression of MMP-3 was observed in pathologic tendons (p=0.06). There were no significant changes in ADAMTS-1, -4, or -5 gene expressions. Discussion These results suggest that the elevated expression of MMP-9 and TIMP-1 genes is likely to reflect the changes in collagen metabolism in pathologic tendons. However, these results also suggest that the proteolysis of proteoglycans in the pathologic tendons is not likely to be affected at the gene expression level of proteinases and their inhibitors. These observations are consistent with others, who showed no difference in the expression of ADAMTS-1, -4, and -5 genes between human Achilles tendons with chronic pain and normal tendons. 2 3 Therefore, it is likely that proteoglycan catabolism is elevated by the activation of ADAMTSs and possibly MMPs and not by increased gene expression. This activation may be driven by growth factors and cytokines such as IL-1α, TGF-β and TNF-α, which are shown to be increased in overuse tendinopathy. However, the details of the mechanisms of these regulatory processes warrant further investigation.

Muskuloskelettaler Ultraschall in der Diagnostik und Therapie von Tendinopathien

“…Die histologischen Veränderungen im Rahmen einer Tendinose stellen sich durch Veränderungen der aktiven metabolischen Zellsysteme dar und können somit bildgebend indirekt detektiert werden. Veränderungen im System der Proteoglykane 9 , 10 führen z. B. zu einer steigenden Wasserbindungsfähigkeit und damit zu einer Dickenzunahme der Sehne ( Abb.…”