MicroRNA-124 inhibits TNF-α- and IL-6-induced osteoclastogenesis
Receptor activator for nuclear factor κB ligand (RANKL)-independent osteoclastogenic pathway was reported recently. MicroRNA (miR)-124 has been known to suppress RANKL-dependent osteoclastogenesis by inhibiting NFATc1 expression. However, whether miR-124 regulates a RANKL-independent pathway has not been elucidated. In this study, we examined whether a RANKL-independent pathway is regulated by miR-124 in addition to the RANKL-dependent one. Using osteoclastogenic culture and pit-formation assay, we found that a miR-124 mimic inhibited osteoclastogenesis in mouse bone marrow-derived macrophages stimulated by TNF-α, IL-6, and M-CSF in the presence of osteoprotegerin. We also showed that the expression levels of osteoclast-specific genes and NFATc1 protein were suppressed in the miR-124 mimic-transfected cells by performing quantitative-polymerase chain reaction and western blotting. Our results indicate that miR-124 is important in inhibiting both RANKL-dependent and -independent osteoclast differentiation by suppressing NFATc1-mediated pathway.
KeywordsMicroRNA-124 Rheumatoid arthritis Osteoclast Tumor necrosis factor-α Interleukin-6 RANKL-independent osteoclastogenesis
We would like to thank Clarity Editing for English proofreading.
Conceptualization: SK. Data curation and making figures and graphs: KO. Formal analysis: SK, JS. Investigation: YN, YN, KU. Methodology: SK, JS, SK. Integration of the study: KO, SK, JS, SK. Supervision: SK. Writing ± original draft: KO. Writing ± review and editing: SK, JS, SK.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest. This study was approved by the Institutional Animal Care and Use Committee of Kobe University.
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