ISG15 Regulates RANKL-Induced Osteoclastogenic Differentiation of RAW264 Cells

• Published in: Biological and Pharmaceutical Bulletin Vol. 38; no. 3; pp. 482 - 486
• Main Authors: Tomoharu Takeuchia, Genki Shimakawaa, Mayumi Tamuraa, Hideyoshi Yokosawab, Yoichiro Arataa
• Format: Journal Article
• Language: Japanese
• Published: Pharmaceutical Society of Japan 01.03.2015
• ISSN: 0918-6158; 1347-5215

Interferon-stimulated gene 15kDa (ISG15) is a protein upregulated by interferon-β that negatively regulates osteoclastogenesis. We investigated the role of ISG15 in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of murine RAW264 cells. RANKL stimulation induced ISG15 expression in RAW264 cells at both the mRNA and protein levels. Overexpression of ISG15 in RAW264 cells resulted in suppression of cell fusion in RANKL-stimulated cells as well as the reduced expression of ATP6v0d2, a gene essential for cell fusion in osteoclastogenic differentiation. These results suggest that ISG15 suppresses RANKL-induced osteoclastogenesis, at least in part, through inhibition of ATP6v0d2 expression. Interferon-α/β is a multifunctional cytokine that exerts various biological functions in immunity, cell differentiation, and so on via the induction of downstream genes called interferon-stimulated genes (ISGs). Interferon-stimulated gene 15kDa (ISG15), a ubiquitin-like protein, is one of the proteins that are most upregulated by interferon stimulation.