miR-21-5p targets SKP2 to reduce osteoclastogenesis in a mouse model of osteoporosis

J Biol Chem. 2021 Jan-Jun:296:100617. doi: 10.1016/j.jbc.2021.100617. Epub 2021 Mar 31.

Abstract

Osteoporosis results from an imbalance between bone formation and bone resorption. Traditional drugs for treating osteoporosis are associated with serious side effects, and thus, new treatment methods are required. This study investigated the role of differentially expressed microRNAs during osteoclast differentiation and osteoclast activity during osteoarthritis as well as the associated underlying mechanisms. We used a microarray to screen microRNAs that decreased in the process of osteoclast differentiation and verified miR-21-5p to decrease significantly using RT-qPCR. In follow-up experiments, we found that miR-21-5p targets SKP2 to regulate osteoclast differentiation. In vivo, ovariectomized mice were used to simulate perimenopausal osteoporosis induced by estrogen deficiency, and miR-21-5p treatment inhibited bone resorption and maintained bone cortex and trabecular structure. These results suggest that miR-21-5p is a new therapeutic target for osteoporosis.

Keywords: SKP2; micro-CT; microRNA; osteoclastogenesis; ovariectomized mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Disease Models, Animal*
  • Female
  • Mice
  • MicroRNAs / genetics*
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • Osteogenesis*
  • Osteoporosis / genetics
  • Osteoporosis / metabolism
  • Osteoporosis / pathology*
  • RAW 264.7 Cells
  • S-Phase Kinase-Associated Proteins / genetics
  • S-Phase Kinase-Associated Proteins / metabolism*

Substances

  • MIRN21 microRNA, mouse
  • MicroRNAs
  • S-Phase Kinase-Associated Proteins