miR‐203‐3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk

The senescence of bone marrow mesenchymal stem cells (BMSCs) contributes to the development of degenerative skeletal conditions. To date, the molecular mechanism resulting in BMSC senescence has not been fully understood. In this study, we identified a small non‐coding RNA, miR‐203‐3p, the expression of which was elevated in BMSCs from aged mice. On the other hand, overexpression of miR‐203‐3p in BMSCs from young mice reduced cell growth and enhanced their senescence. Mechanistically, PDZ‐linked kinase (PBK) is predicted to be the target of miR‐203‐3p. The binding of miR‐203‐3p to Pbk mRNA could decrease its expression, which in turn inhibited the ubiquitination‐mediated degradation of p53. Furthermore, the intravitreal injection of miR‐203‐3p‐inhibitor into the bone marrow cavity of aged mice attenuated BMSC senescence and osteoporosis in aged mice. Collectively, these findings suggest that targeting miR‐203‐3p to delay BMSC senescence could be a potential therapeutic strategy to alleviate age‐related osteoporosis. This study indicates that inhibiting miR‐203‐3p (partly via the PBK/p53 signaling pathway) improves cell growth dynamics and slows the process of cellular senescence, rejuvenating senescent BMSCs. Furthermore, it presents a new potential target for delaying age‐related osteoporosis.