circ_0029463 promotes osteoclast differentiation by mediating miR-134-5p/Rab27a axis

J Orthop Surg Res. 2024 Feb 7;19(1):128. doi: 10.1186/s13018-024-04610-5.

Abstract

Objective: Osteoporosis is the imbalance in bone homeostasis between osteoblasts and osteoclasts. In this study, we investigated the effects of the circ_0029463/miR-134-5p/Rab27a axis on RANKL-induced osteoclast differentiation.

Methods: RT-qPCR and western blotting were used to detect the expression of circ_0029463, miR-134-5p, and Rab27a in tissues from patients with osteoporosis and in RANKL-induced osteoclasts. Osteoclast differentiation was verified by TRAP staining. Osteoclast biomarkers, including NFATc1, TRAP, and CTSK, were measured. The target and regulatory relationships between circ_0029463, miR-134-5p, and the Rab27a axis were verified using RIP, dual-luciferase reporter gene, and RNA pull-down assays.

Results: Elevated expression of circ_0029463 and Rab27a and decreased miR-134-5p expression were observed in the tissues of patients with osteoporosis, and a similar expression pattern was observed in RANKL-induced osteoclasts. Suppression of circ_0029463 expression or miR-134-5p overexpression curbed RANKL-induced osteoclast differentiation, whereas such an effect was abolished by Rab27 overexpression. circ_0029463 sponges miR-134-5p to induce Rab27a expression.

Conclusion: circ_0029463 sponges miR-134-5p to abolish its suppressive effect of miR-134-5p on Rab27a expression, thereby promoting osteoclast differentiation.

Keywords: Osteoclast differentiation; Rab27a; circ_0029463; miR-134-5p.

MeSH terms

  • Blotting, Western
  • Cell Proliferation
  • Humans
  • MicroRNAs* / genetics
  • Osteoblasts
  • Osteoclasts
  • Osteoporosis*
  • RNA, Circular / genetics

Substances

  • MicroRNAs
  • MIRN134 microRNA, human
  • RNA, Circular
  • RAB27A protein, human