miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1.

ABSTRACT

Tendon stem/progenitor cell (TSPC) senescence may lead to age-related tendon disorders and impair tendon regeneration and replacement capacity in humans. However, the mechanisms governing TSPC aging and degeneration remain obscure. Recently, it has been reported that Rho-associated coiled-coil protein kinase 1 (ROCK1) might be a key player in TSPC aging process. miRNAs are also involved in cellular senescence. In this study, whether miRNAs modulate senescence of TSPCs through targeting ROCK1 was evaluated. We found that miR-135a, which directly binds to the 3'-untranslated region of ROCK1, is significantly downregulated in aged compared with young TSPCs. Overexpression of miR-135a in young TSPCs suppresses senescence, promotes proliferation, and induces migration and tenogenic differentiation, whereas suppression of miR-135a in aged TSPCs has the opposite effects. By gain-of-function and loss-of-function studies, we confirmed that ROCK1 mediates the effects of miR-135a in TSPCs. Taken together, our data suggest that miR-135a plays an important role in TSPC senescence via targeting ROCK1.