MiR-146a induces the aging of mesenchymal stem cell via CASK

Mesenchymal stem cell (MSC) has elicited great hopes for regenerative medicine, however, its regenerative potential decreases with age, which raises questions about the efficiency of autologous transplantations in elderly patients. To elucidate the cellular consequences and epigenetic mechanisms of aging, the functional and epigenetic changes in bone marrow derived MSC (BMSC) from normal and aging rats were studied concurrently. The results demonstrate that the proliferation and differentiation abilities of BMSCs from aging rats declined compared with those from young rats. In order to identify which miRNA involve in the senescence of BMSC, miRNA expression profiles of both BMSCs from young and aging rats were examined. The results showed that miR-146a expression increased significantly in BMSCs from aging rats compared with that from young rats, following with a decrease in Calcium/calmodulin-dependent Serine protein kinase (CASK) expression. Inhibition of miR-146a can reduces the numbers of senescent cells and stimulates the differentiation of BMSC. Luciferase assay demonstrated that CASK was a direct target of miR-146a, inhibition of miR-146a significantly elevated the expression of CASK. Overexpression of CASK in aged BMSC can rescue its proliferation and differentiation abilities. All these results indicate that miR-146a may cause aging and senescence of BMSC through the inhibition of CASK expression, which may be potential target for BMSC aging and some age-related disease.