MicroRNA-124 inhibits TNF-α- and IL-6-induced osteoclastogenesis

Rheumatol Int. 2019 Apr;39(4):689-695. doi: 10.1007/s00296-018-4218-7. Epub 2018 Dec 14.

Abstract

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.

Keywords: Interleukin-6; MicroRNA-124; Osteoclast; RANKL-independent osteoclastogenesis; Rheumatoid arthritis; Tumor necrosis factor-α.

MeSH terms

  • Animals
  • Interleukin-6 / metabolism
  • Macrophage Colony-Stimulating Factor / metabolism
  • Macrophages / metabolism*
  • Mice
  • MicroRNAs / genetics*
  • NFATC Transcription Factors / metabolism
  • Osteogenesis / genetics*
  • Osteoprotegerin / metabolism
  • RANK Ligand
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • MicroRNAs
  • Mirn124 microRNA, mouse
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Osteoprotegerin
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Macrophage Colony-Stimulating Factor