Repetitive mechanical stretching modulates transforming growth factor-β induced collagen synthesis and apoptosis in human patellar tendon fibroblasts

摘要

The cellular and molecular mechanisms underlying the development of tendinopathy are not clear, but inflammatory mediators produced by tendon fibroblasts in response to repetitive mechanical loading may be an important factor for this illness. In this study, we explored the effect of cyclic mechanical stretching on collagen synthesis and apoptosis of human patellar tendon fibroblasts (HPTFs). The role of a candidate inflammatory mediator, transforming growth factor-β1 (TGFβ1), which we identified in a cytokine antibody array, in collagen synthesis and apoptosis during repetitive mechanical stretching was also investigated. Our results showed that there was a significant increase in collagen type I synthesis at 4% and 8% stretch. Significantly, enhancement of apoptosis may account for the observed decrease in fibroblast numbers after 8% stretching. Furthermore, the exogenous addition of an anti-TGFβ1 antibody or gene silencing by si-TGFβ1 eliminated the increase in collagen type I production and activities of caspases during apoptosis under cyclic uniaxial stretching conditions. These results suggest that TGFβ1 may take part in the increase of cellular production of collagen type I and apoptosis during the development of tendinopathy. Furthermore, caspase 8 mediates activation of caspase 3 and poly ADP-ribose polymerase (PARP) cleavage during TGFβ1-induced apoptosis in stretching HPTFs.