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

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.

• Authors: Qin Sun, Boran Zhang, Wei Zhu, Wei Wei, Jingzhi Ma, Franklin R Tay
• Journal: Journal of dentistry (J Dent) Vol. 82 Pg. 91-97 (03 2019) ISSN: 1879-176X [Electronic] England
• PMID: 30716449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Ltd.

Chemical References

• MicroRNAs
• Mirn338 microRNA, mouse

Topics

• Animals
• Cell Differentiation (genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Developmental (genetics)
• Mice
• MicroRNAs (metabolism)
• Osteoclasts (cytology)
• Osteogenesis (genetics)
• Osteoporosis (genetics, prevention & control)
• RAW 264.7 Cells