UBC Theses and Dissertations
The potential role of MMP2 in the response of tendons to mechanical stimulation Huisman, Elise Suzanne
Tendinopathy is a common problem in the population leaving people in pain, unable to work or be physically active. High levels of musculotendinous strain (resulting from heavy lifting or obesity) and repetitive movements are risk factors for tendinopathy. Because MMPs and TIMPs play a crucial role in the repair, remodeling, and degeneration of collagen fibers in tendon, the aim of this dissertation was to identify the potential roles of MMPs, TIMPs and collagens type I and III, using in-vitro and in-vivo models of overuse and repair. Having identified a potential role of MMP2 in these laboratory models, a clinical study was also conducted to evaluate the serum levels of MMPs and TIMPs in patients who had experienced Achilles tendon rupture. Cultured tendon cells, controlled by high frequency or high strain stimulation, simulating overuse, increased MMP2 mRNA expression. Collagen type I mRNA and protein levels were increased in cultured tendon cells by controlled mechanical stimulation with intermittent rest periods compared to continuous mechanical stimulation. In both the normal healthy rabbit and an overuse model of the rabbits’ Achilles tendon, regional differences in mRNA expression and histological structure were observed. After two weeks of repetitive tendon loading, collagen intensity, measured by second harmonic generation microscopy, was decreased in the flexor digitorum superficialis (FDS) tendon compared to the contralateral FDS tendon and healthy control FDS tendon, indicating damage or remodelling of the collagen in response to overuse. Structural changes were observed locally, combined with elevated tissue MMP2 protein levels suggesting a possible contribution of MMP2 to the development of early collagen degradation. MMP2 appears to play a role early in the response of tendon to repetitive loading. It is detectable in serum after 1 week of overuse, and high repetition number and high strain level are independent modulators of MMP2 expression in tenocytes. However, MMP2 levels in serum decline to baseline after 2 weeks in the animal model, and were downregulated compared to controls in patients with a more Achilles tendon rupture. Further research into the specific processes of tendon injury and repair played by MMP2 are warranted.
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