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Osteoclasts in the Inflammatory Arthritis: Implications for Pathologic Osteolysis

  • Youn-Kwan Jung (Biomedical Research Institute, Gyeongsang National University Hospital) ;
  • Young-Mo Kang (Division of Rheumatology, Department of Internal medicine, Kyungpook National University Hospital) ;
  • Seungwoo Han (Division of Rheumatology, Department of Internal medicine, Kyungpook National University Hospital)
  • Received : 2018.12.29
  • Accepted : 2019.02.17
  • Published : 2019.02.28
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Abstract

The enhanced differentiation and activation of osteoclasts (OCs) in the inflammatory arthritis such as rheumatoid arthritis (RA) and gout causes not only local bone erosion, but also systemic osteoporosis, leading to functional disabilities and morbidity. The induction and amplification of NFATc1, a master regulator of OC differentiation, is mainly regulated by receptor activator of NF-κB (RANK) ligand-RANK and calcium signaling which are amplified in the inflammatory milieu, as well as by inflammatory cytokines such as TNFα, IL-1β and IL-6. Moreover, the predominance of CD4+ T cell subsets, which varies depending on the condition of inflammatory diseases, can determine the fate of OC differentiation. Anti-citrullinated peptide antibodies which are critical in the pathogenesis of RA can bind to the citrullinated vimentin on the surface of OC precursors, and in turn promote OC differentiation and function via IL-8. In addition to adaptive immunity, the activation of innate immune system including the nucleotide oligomerization domain leucine rich repeat with a pyrin domain 3 inflammasome and TLRs can regulate OC maturation. The emerging perspectives about the diverse and close interactions between the immune cells and OCs in inflammatory milieu can have a significant impact on the future direction of drug development.

Keywords

Acknowledgement

This research was supported by a grant to S.H. from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant numbers NRF-2016R1D1A1B03932036).

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