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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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IRF2 enhances RANKL-induced osteoclast differentiation via regulating NF-κB/NFATc1 signaling

  • Kim, Inyoung (Department of Pharmacology, Chonnam National University Medical School) ;
  • Kim, Jung Ha (Department of Pharmacology, Chonnam National University Medical School) ;
  • Kim, Kabsun (Department of Pharmacology, Chonnam National University Medical School) ;
  • Seong, Semun (Department of Pharmacology, Chonnam National University Medical School) ;
  • Lee, Keun-Bae (Department of Orthopedic Surgery, Chonnam National University Medical School and Hospital) ;
  • Kim, Nacksung (Department of Pharmacology, Chonnam National University Medical School)
  • Received : 2021.05.31
  • Accepted : 2021.08.19
  • Published : 2021.09.30
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Abstract

Interferon regulatory factors (IRFs) play roles in various biological processes including cytokine signaling, cell growth regulation and hematopoietic development. Although it has been reported that several IRFs are involved in bone metabolism, the role of IRF2 in bone cells has not been elucidated. Here, we investigated the involvement of IRF2 in RANKL-induced osteoclast differentiation. IRF2 overexpression in osteoclast precursor cells enhanced osteoclast differentiation by regulating the expression of NFATc1, a master regulator of osteoclastogenesis. Conversely, IRF2 knockdown inhibited osteoclast differentiation and decreased the NFATc1 expression. Moreover, IRF2 increased the translocation of NF-κB subunit p65 to the nucleus in response to RANKL and subsequently induced the expression of NFATc1. IRF2 plays an important role in RANKL-induced osteoclast differentiation by regulating NF-κB/NFATc1 signaling pathway. Taken together, we demonstrated the molecular mechanism of IRF2 in osteoclast differentiation, and provide a molecular basis for potential therapeutic targets for the treatment of bone diseases characterized by excessive bone resorption.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MIST) (NRF-2019R1A5A2027521 and 2020R1I1A1A01061781), and the Chonnam National University Hospital Biomedical Research Institute (BCRI20046).

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