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The influence of interleukin-32γ on osteoclastogenesis with a focus on fusion-related genes

Yong-Gil Kim1, Min Wook So, Bon San Koo

  • 1Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul, 138-736, South Korea.

Journal of Clinical Immunology
|November 10, 2011
PubMed

We previously reported that interleukin-32 gamma (IL-32γ) has a direct effect on osteoclast differentiation and activation in vitro in the context of receptor activator of NF-κB ligand (RANKL) co-stimulation. However, the stage of osteoclast differentiation at which IL-32γ exerts its effect was not determined. Here, we demonstrated that IL-32γ plays an important role in the fusion of preosteoclasts to yield multinuclear osteoclasts, particularly large osteoclasts. The synergistic effect of IL-32γ on RANKL-induced formation of multinuclear osteoclasts was readily apparent when cells were treated with IL-32γ at the fusion stage. In addition, we demonstrated that IL-32γ induced the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and NFATc1 inactivation by cyclosporine treatment attenuated the effect of IL-32γ. These results indicate that IL-32γ is a potential mediator of osteoclast fusion, likely through up-regulation of NFATc1 and DC-STAMP.

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