The lncRNA Rhno1/miR-6979-5p/BMP2 Axis Modulates Osteoblast Differentiation

Int J Biol Sci. 2020 Mar 12;16(9):1604-1615. doi: 10.7150/ijbs.38930. eCollection 2020.

Abstract

The roles of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) as regulators of mRNA expression in various diseases have recently been reported. Osteoblast differentiation is the vital process which mediates bone formation and fracture healing. In present study, we found microRNA-6979-5p (miR-6979-5p) to be the most differentially expressed miRNA between normal bone and calluses of mice, and overexpression of miR-6979-5p was negatively associated with osteoblast differentiation. Through luciferase assays, we found evidence that bone morphogenetic protein 2 (BMP2) is a miR-6979-5p target gene that positively regulates osteoblast differentiation. We further identified the lncRNA Rhno1 as a competing endogenous RNA (ceRNA) of miR-6979-5p, and we verified that it was able to influence osteoblast differentiation both in vitro and in vivo. In summary, our data indicates that the lncRNA Rhno1/miR-6979-5p/BMP2 axis is a significant regulatory mechanism controlling osteoblast differentiation, and it may thus offer a novel therapeutic strategy for fracture healing.

Keywords: BMP2; Fracture; LncRNA; mRNA; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / genetics*
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Differentiation / genetics*
  • Fracture Healing / genetics
  • Gene Expression Regulation*
  • Male
  • Mice, Inbred C57BL
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • RNA, Long Noncoding / metabolism*

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • RNA, Long Noncoding