MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway.

Abstract

Osteoporosis (OP) has the characteristics of the decline in bone mineral density and worsening of bone quality, contributing to a higher risk of fractures. Some microRNAs (miRNAs) have been validated as possible mediators of osteoblast differentiation. We herein aimed to clarify whether miR-497-5p regulates the differentiation of osteoblasts in MC3T3-E1 cells. The expression of miR-497-5p in OP patients and controls was measured by RT-qPCR, and its expression changes during osteoblast differentiation were determined as well. The effects of miR-497-5p on the differentiation of MC3T3-E1 cells were studied using MTT, ALR staining, and ARS staining. The target gene of miR-497-5p was predicted by TargetScan, and the effects of its target gene on differentiation and the pathway involved were investigated. miR-497-5p expressed poorly in OP patients, and its expression was upregulated during MC3T3-E1 cell differentiation. Overexpression of miR-497-5p promoted mineralized nodule formation and the expression of RUNX2 and OCN. miR-497-5p targeted high mobility group AT-Hook 2 (HMGA2), while the upregulation of HMGA2 inhibited osteogenesis induced by miR-497-5p mimic. miR-497-5p significantly impaired the c-Jun NH2-terminal kinase (JNK) pathway, whereas HMGA2 activated this pathway. Activation of the JNK pathway inhibited the stimulative role of miR-497-5p mimic in osteogenesis. miR-497-5p inhibits the development of OP by promoting osteogenesis via targeting HMGA2.