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

Journal of Orthopaedic Surgery and Research

Yexiang Yang¹  Yang Wang²  Huiqing Zhao²  Xiaolei Feng²  Adi Deng²  Biying Chen²  Zhaolan Ou³ 

[1] Department of Joint and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, 510630, Guangzhou, Guangdong, People’s Republic of China;Department of Orthopaedics, The Third Affiliated Hospital of Sun Yat-Sen University, No, 2693, Kaichuang Road, 510530, Guangzhou, Guangdong, People’s Republic of China;Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No, 600, Tianhe Road, Tianhe District, 510630, Guangzhou, Guangdong, People’s Republic of China;

关键词: MicroRNA-497-5p;    HMGA2;    JNK pathway;    Osteoporosis;    Osteoblasts;   

DOI  :  10.1186/s13018-020-02043-4

来源: Springer

【 摘 要 】

BackgroundOsteoporosis (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.MethodsThe 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.ResultsmiR-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.ConclusionsmiR-497-5p inhibits the development of OP by promoting osteogenesis via targeting HMGA2.

【 授权许可】

CC BY