lncRNA-Gm5532 regulates osteoclast differentiation through the miR-125a-3p/TRAF6 axis

Acta Biochim Biophys Sin (Shanghai). 2024 Jan 25;56(1):54-61. doi: 10.3724/abbs.2023245.

Abstract

Long noncoding RNAs (lncRNAs) are important regulators of bone metabolism. In this study, lncRNA microarray analysis was used to identify differentially expressed lncRNAs in differentiated osteoclasts. lncRNA-Gm5532 is highly expressed during osteoclast differentiation. lncRNA-Gm5532 knockdown impairs osteoclast formation and bone resorption. Mechanistic experiments show that lncRNA-Gm5532 functions as a competing endogenous RNA (ceRNA) and acts as a sponge for miR-125a-3p, which promotes TNF receptor-associated factor 6 (TRAF6) expression. miR-125a-3p mimics suppress osteoclast differentiation and TAK1/NF-κB/MAPK signaling. The miR-125a-3p inhibitor reverses the negative effects of siGm5532 on osteoclast differentiation. In summary, our study reveals that lncRNA-Gm5532 functions as an activator in osteoclast differentiation by targeting the miR-125a-3p/TRAF6 axis, making it a novel biomarker and potential therapeutic target for osteoporosis.

Keywords: TNF receptor-associated factor 6 (TRAF6); lncRNA-Gm5532; miR-125a-3p; osteoclast differentiation.

MeSH terms

  • Bone Resorption* / genetics
  • Bone Resorption* / metabolism
  • Humans
  • MicroRNAs* / metabolism
  • Osteoclasts / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • TNF Receptor-Associated Factor 6

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (No. 82060168), the Guizhou Education Department Youth Science and Technology Talents Growth Project (No. Qian Jiao He KY Zi [2021]199), and the Guizhou Provincial Science and Technology Foundation (No. Qian Ke He Ji Chu-ZK[2021]-Yi Ban 398).