MiR-142-5p promotes bone repair by maintaining osteoblast activity

J Bone Miner Metab. 2017 May;35(3):255-264. doi: 10.1007/s00774-016-0757-8. Epub 2016 Apr 16.

Abstract

MicroRNAs play important roles in regulating bone regeneration and remodeling. However, the pathophysiological roles of microRNAs in bone repair remain unclear. Here we identify a significant upregulation of miR-142-5p correlated with active osteoblastogenesis during the bone healing process. In vitro, miR-142-5p promoted osteoblast activity and matrix mineralization by targeting the gene encoding WW-domain-containing E3 ubiquitin protein ligase 1. We also found that the expression of miR-142-5p in the callus of aged mice was lower than that in the callus of young mice and directly correlated with the age-related delay in bone healing. Furthermore, treatment with agomir-142-5p in the fracture areas stimulated osteoblast activity which repaired the bone fractures in aged mice. Thus, our study revealed that miR-142-5p plays a crucial role in healing fractures by maintaining osteoblast activity, and provided a new molecular target therapeutic strategy for bone healing.

Keywords: Bone fracture; MicroRNA; Osteoblastogenesis; Wwp1.

MeSH terms

  • Animals
  • Antagomirs / metabolism
  • Base Sequence
  • Bone Matrix / metabolism
  • Bone and Bones / metabolism
  • Bone and Bones / pathology*
  • Bony Callus / pathology
  • Calcification, Physiologic / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology*
  • Osteogenesis / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Wound Healing / genetics*

Substances

  • Antagomirs
  • MicroRNAs
  • Mirn142 microRNA, mouse
  • WWP1 protein, mouse
  • Ubiquitin-Protein Ligases