Reciprocal effect of microRNA-224 on osteogenesis and adipogenesis in steroid-induced osteonecrosis of the femoral head

• Published in: Bone (New York, N.Y.) Vol. 145; p. 115844
• Main Authors: Cao, Yuanwu, Jiang, Chang, Wang, Xinyuan, Wang, Hao, Yan, Zuoqin, Yuan, Hengfeng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2021
• Subjects: Adipogenesis; BMSCs; microRNA-224; Osteogenesis; Osteonecrosis; Osteonecrosis; microRNA-224; Osteogenesis; BMSCs; Adipogenesis
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2021.115844

The adverse effects of glucocorticoids (GCs) on bone marrow stromal stem cells (BMSCs) play an important role in steroid-induced osteonecrosis of the femoral head (ONFH). Our previous miRNA microarray analysis indicated that microRNA-224-5p (miR-224-5p) could be a potential regulator; however, the underlying mechanism remains unclear. In the present study, we demonstrated that miR-224-5p was upregulated in GC-treated BMSCs, and functional experiments revealed that miR-224-5p could suppress osteogenic but promote adipogenic differentiation of BMSCs. Smad4 was identified as a direct target gene of miR-224-5p, and the Smad4-Taz axis was confirmed as the regulatory pathway for adipo-osteogenic differentiation of BMSCs. Our in vivo experiments further confirmed that the miR-224-5p antagomir could alleviate the inhibitory effects of GCs and facilitate bone formation in steroid-induced ONFH models. Therefore, these findings provide insight into the function of miR-224-5p as a reciprocal regulator of the adipo-osteogenic differentiation of BMSCs, and it could serve as a novel therapeutic target for steroid-induced ONFH. •miR-224-5p serves as a reciprocal regulator of the adipo-osteogenic differentiation of BMSCs.•Smad4-TAZ axis is the intrinsic regulator of miR-224-5p in osteogenesis and adipogenesis.•Inhibition of miR-224-5p reduces the degree and incidence of steroid-induced ONFH.