MiR-143 Promotes Osteoblast Differentiation by Targeting HDAC7

Abstract

Molecular mechanisms in the regulation of osteoblast development are still largely elusive, and the roles of microRNAs in this process have attracted much attention. In this study, we found that miR-143 expression levels were significantly increased during osteoblast formation in MC3T3-E1 cells, and serum miR-143 expression levels were negatively correlated with increasing age in humans, suggesting the potential roles of miR-143 in osteoblast development. Overexpression of miR-143 promoted osteoblast formation in MC3T3-E1 cells, while its inhibition suppressed osteoblast formation. Furthermore, we constructed miR-143 knockout mice and found that the bone volume was significantly decreased while osteoblast development was markedly inhibited by miR-143 knockout, determining its roles in the regulation of osteoblast development. Mechanistically, the osteoblast development inhibitor HDAC7 was identified as the direct target of miR-143, and knockdown of HDAC7 was found to rescue the function of miR-143 deficiency in mice. Thus, miR-143 promotes osteoblast development by directly targeting HDAC7. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81572637, No. 81702666, No. 81272942, No. 81202122, and No. 30973019). Declaration of Interests: The authors indicate no potential conflicts of interest. Ethics Approval Statement: The clinical study was approved by the Committees of Clinical Ethics of the Shanghai Changhai Hospital, Second Military Medical University, and we obtained informed consent from the participants.