Fluid shear stress regulates osteoblast proliferation and apoptosis via the lncRNA TUG1/miR-34a/FGFR1 axis

J Cell Mol Med. 2021 Sep;25(18):8734-8747. doi: 10.1111/jcmm.16829. Epub 2021 Aug 5.

Abstract

LncRNAs and microRNAs play critical roles in osteoblast differentiation and bone formation. However, their exact roles in osteoblasts under fluid shear stress (FSS) and the possible mechanisms remain unclear. The aim of this study was to explore whether and how miR-34a regulates osteoblast proliferation and apoptosis under FSS. In this study, FSS down-regulated miR-34a levels of MC3T3-E1 cells. MiR-34a up-regulation attenuated FSS-induced promotion of proliferation and suppression of apoptosis. Luciferase reporter assay revealed that miR-34a directly targeted FGFR1. Moreover, miR-34a regulated osteoblast proliferation and apoptosis via FGFR1. Further, we validated that lncRNA TUG1 acted as a competing endogenous RNA (ceRNA) to interact with miR-34a and up-regulate FGFR1 protein expression. Furthermore, lncRNA TUG1 could promote proliferation and inhibit apoptosis. Taken together, our study revealed the key role of the lncRNA TUG1/miR-34a/FGFR1 axis in FSS-regulated osteoblast proliferation and apoptosis and may provide potential therapeutic targets for osteoporosis.

Keywords: FGFR1; apoptosis; fluid shear stress; lncRNA TUG1; miR-34a; osteoblast; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / metabolism*
  • Osteoblasts* / cytology
  • Osteoblasts* / metabolism
  • RNA, Long Noncoding / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism*
  • Stress, Mechanical

Substances

  • MIRN34a microRNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA TUG1, mouse
  • Fgfr1 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1