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

MicroRNA-497-5p通过HMGA2介导的JNK信号通路促进成骨细胞分化

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作者:Huiqing Zhao, Yexiang Yang, Yang Wang, Xiaolei Feng, Adi Deng, Zhaolan Ou, Biying Chen

Background

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.

Conclusions

miR-497-5p inhibits the development of OP by promoting osteogenesis via targeting HMGA2.

Methods

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.

Results

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. Conclusions: miR-497-5p inhibits the development of OP by promoting osteogenesis via targeting HMGA2.

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