Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins

David E. Place, R. K. Subbarao Malireddi, Jieun Kim, Peter Vogel, Masahiro Yamamoto and Thirumala-Devi Kanneganti ()
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David E. Place: St. Jude Children’s Research Hospital
R. K. Subbarao Malireddi: St. Jude Children’s Research Hospital
Jieun Kim: St. Jude Children’s Research Hospital
Peter Vogel: St. Jude Children’s Research Hospital
Masahiro Yamamoto: Osaka University
Thirumala-Devi Kanneganti: St. Jude Children’s Research Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract Chronic inflammation during many diseases is associated with bone loss. While interferons (IFNs) are often inhibitory to osteoclast formation, the complex role that IFN and interferon-stimulated genes (ISGs) play in osteoimmunology during inflammatory diseases is still poorly understood. We show that mice deficient in IFN signaling components including IFN alpha and beta receptor 1 (IFNAR1), interferon regulatory factor 1 (IRF1), IRF9, and STAT1 each have reduced bone density and increased osteoclastogenesis compared to wild type mice. The IFN-inducible guanylate-binding proteins (GBPs) on mouse chromosome 3 (GBP1, GBP2, GBP3, GBP5, GBP7) are required to negatively regulate age-associated bone loss and osteoclastogenesis. Mechanistically, GBP2 and GBP5 both negatively regulate in vitro osteoclast differentiation, and loss of GBP5, but not GBP2, results in greater age-associated bone loss in mice. Moreover, mice deficient in GBP5 or chromosome 3 GBPs have greater LPS-mediated inflammatory bone loss compared to wild type mice. Overall, we find that GBP5 contributes to restricting age-associated and inflammation-induced bone loss by negatively regulating osteoclastogenesis.

Date: 2021
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DOI: 10.1038/s41467-020-20807-8

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