MicroRNA-532-5p is implicated in the regulation of osteoporosis by forkhead box O1 and osteoblast differentiation

• Published in: BMC musculoskeletal disorders Vol. 21; no. 1; pp. 296 - 8
• Main Authors: Guo, Xinyu, Wei, Shijun, Xu, Feng, Cai, Xianhua, Wang, Huasong, Ding, Ran
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.05.2020; BioMed Central; BMC
• Subjects: Aged; Alkaline phosphatase; Alkaline Phosphatase - metabolism; Analysis; Binding sites; Bioinformatics; Bones; Cartilage diseases; Cell Differentiation - genetics; Cell Line; Collagen; Collagen (type I); Collagen Type I - metabolism; Disease; Female; Forkhead Box Protein O1 - genetics; Forkhead Box Protein O1 - metabolism; Forkhead protein; FOXO1; FOXO1 protein; Fractures; Gene expression; Genes; Health aspects; Hormone replacement therapy; Humans; Metabolism; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-532-5p; miRNA; Osteoarthritis; Osteoblastogenesis; Osteoblasts - metabolism; Osteocalcin; Osteocalcin - metabolism; Osteogenesis; Osteogenesis - genetics; Osteogenic differentiation; Osteoporosis; Osteoporosis - metabolism; Phosphatases; Polymerase chain reaction; Proteins; Signal transduction; Software; Therapeutic applications; Transfection; Up-Regulation; China; United States > US; Osteoporosis; Osteogenic differentiation; miR-532-5p; FOXO1
• ISSN: 1471-2474; 1471-2474
• DOI: 10.1186/s12891-020-03317-y

MicroRNAs (miRNAs) are critical regulators in osteogenesis and cartilage formation. This study was designed to investigate whether miR-532-5p plays a role in the regulation of osteoporosis. Osteoporotic fractures (OP group, n = 10) or osteoarthritis without osteoporosis (control group, n = 10) were selected as subjects in this study. Quantitative analysis of gene expression was performed by RT-PCR. Western blot was used to determine the expression levels of protein forkhead O1 (FOXO1). Bioinformatics analyses and luciferase reporter assay were used to verify the downstream target of miR-532-5p. Compared with the non-osteoporotic controls, miR-532-5p was upregulated in osteoporotic samples, and expression of miR-532-5p was downregulated in the osteogenic C2C12 cell model. Overexpression of miR-532-5p resulted in decreased expression levels of key osteoblast markers, including alkaline phosphatase (ALP), osteocalcin (OC), and collagen type I alpha 1 (COL1A1). The inhibitory results of miR-532-5p were reversed. MiR-532-5p contained a putative FOXO1 binding site. Moreover, miR-532-5p inhibited the expression of FOXO1, and overexpression of FOXO1 inhibited the effect of miR-532-5p on osteoblast markers. MiR-532-5p can provide references to osteoporosis by regulating the expression of FOXO1 and osteoblast differentiation. MiR-532-5p might serve as a therapeutic target for osteoporosis.