A potential therapeutic target for regulating osteoporosis via suppression of osteoclast differentiation

Qin Sun, Boran Zhang, Wei Zhu, Wei Wei, Jingzhi Ma, Franklin Chi Meng Tay

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objectives: Osteoclast differentiation is regulated by transcriptional, post-transcriptional and post-translational mechanisms. Micro-ribonucleic acids (miRNAs) are 20–24 nucleotides long non-coding RNAs involved in post-translational regulation of gene expressions during osteoclast differentiation. The objective of the present study was to investigate the role played by the miRNA, miR-338-3p, in osteoclastogenesis. Methods: Osteoclastogenesis was induced in murine RAW264.7 cells using M-CSF and RANKL. The differentiated cells were harvested at designated times for TRAP staining and detection of designated gene expressions. A synthetic miR-338-3p mimic or its inhibitor was transfected into RAW264.7 cells prior to the induction of osteoclastogenesis. The effects of mimic or inhibitor on osteoclastogenesis were examined by qRT-PCR and TRAP staining. Bioinformatic analysis and luciferase activity were performed to identify the relationship between miR-338-3p and the transcription factor MafB. The miR-338-3p mimic and MafB siRNA were co-transfected into RAW264.7 cells to evaluate the cross-talk between miR-338-3p and MafB. Results: miR-338-3p was increased significantly during osteoclast differentiation. Overexpression of miR-338-3p promoted osteoclastogenesis while its inhibition had the opposite effect. Bioinformatic analysis and dual luciferase assays indicated that miR-338-3p targeted MafB to repress its gene expression. MafB knockdown by RNA silencing blocked the promotional effect of miR-338-3p on osteoclast differentiation. Conclusion: Because miR-338-3p is crucial for osteoclastic differentiation via targeting of the transcription factor MafB, inhibition of this miRNA represents a potential strategy for modulating osteoporosis in an aging population. Clinical significance: Understanding the role played by miR-338-3p in osteoclast differentiation bridges the gap between the pathogenesis of osteoporosis and the quest for novel therapeutics to reduce the risk of bone fracture associated with this global disease.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalJournal of Dentistry
Volume82
DOIs
StatePublished - Mar 2019

Keywords

  • Osteoclasts
  • Osteoporosis
  • Transcription factor MafB
  • Transfection
  • microRNA

ASJC Scopus subject areas

  • Dentistry(all)

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