Rheumatology International

, Volume 39, Issue 4, pp 689–695 | Cite as

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

  • Kenichiro Ohnuma
  • Shimpei Kasagi
  • Kenichi Uto
  • Yoriko Noguchi
  • Yuji Nakamachi
  • Jun Saegusa
  • Seiji KawanoEmail author
Bone and Cartilage


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.


MicroRNA-124 Rheumatoid arthritis Osteoclast Tumor necrosis factor-α Interleukin-6 RANKL-independent osteoclastogenesis 



We would like to thank Clarity Editing for English proofreading.

Author contributions

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.

Supplementary material

296_2018_4218_MOESM1_ESM.pptx (40 kb)
Supplementary material 1 (PPTX 41 KB)
296_2018_4218_MOESM2_ESM.pptx (39 kb)
Supplementary material 2 (PPTX 39 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kenichiro Ohnuma
    • 1
    • 2
  • Shimpei Kasagi
    • 1
    • 2
  • Kenichi Uto
    • 2
  • Yoriko Noguchi
    • 2
  • Yuji Nakamachi
    • 2
  • Jun Saegusa
    • 1
    • 2
  • Seiji Kawano
    • 1
    Email author
  1. 1.Division of Laboratory MedicineKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of Clinical LaboratoryKobe University HospitalKobeJapan

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