MicroRNA-582-3p regulates osteoporosis through regulating homeobox A10 and osteoblast differentiation

Immunopharmacol Immunotoxicol. 2022 Jun;44(3):421-428. doi: 10.1080/08923973.2022.2052895. Epub 2022 Mar 30.

Abstract

Objective: Recent studies have demonstrated that micro RNAs (miRNAs) are involved in bone formation and bone cell differentiation, but the role of miR-582-3p in osteoporosis is unclear. We want to study the mechanism of miR-582-3p on osteogenic differentiation.

Method: The expression of miR-582-3p and homeobox (Hox) A10 were analyzed by quantitative RT-PCR. The expression levels of HOXA10 protein were determined by Western blot. The target of HOXA10 was identified by bioinformatics and luciferase reporter gene assay.

Results: The results showed that miR-582-3p was up-regulated in OP tissues and down-regulated in osteogenic differentiated C2C12 cells compared with that in the control group. Overexpression of miR-582-3p resulted in reduced expression levels of osteocalcin (OC), alkaline phosphatase (ALP), and collagen, type I, α1 (COL1A1). miR-582-3p had a potential binding site with HOXA10. Moreover, miR-582-3p inhibited the expression of HOXA10, and overexpression of HOXA10 reduced the effect of miR-582-3p on osteoblast markers. HOXA10 was the target gene of miR-582-3p, which could inhibit the expression of HOXA10. Furthermore, HOXA10 reduced the role of miR-582-3p in osteoblast markers. miR-582-3p inhibited the development of osteoporosis by regulating HOXA10 and osteoblast differentiation.

Conclusions: miR-582-3p may be a therapeutic target of osteoporosis treatment.

Keywords: HOXA10; miRNA-582-3p; osteogenic differentiation; osteoporosis.

MeSH terms

  • Cell Differentiation / genetics
  • Genes, Homeobox
  • Homeobox A10 Proteins / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteoblasts / metabolism
  • Osteogenesis / genetics
  • Osteoporosis* / genetics
  • Osteoporosis* / metabolism

Substances

  • Homeobox A10 Proteins
  • MIRN582 microRNA, human
  • MicroRNAs