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HOME > News & Topics > Research > FY 2013 > Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP (Shizuo AKIRA in JEM)

Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP (Shizuo AKIRA in JEM)

Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to RANKL. The authors found that RANKL induced expression of the DExD/H helicase family corepressor strawberry notch homologue 2 (Sbno2). Previous in vitro studies showed that Sbno2 is induced by IL-10 and is involved in NF-kB repression. However, the role of Sbno2 in vivo and its pleiotropic functions are unknown. Sbno2 gene targeting resulted in normal NF-kB activation by TLR ligands. However, Sbno2-deficient mice exhibited increased bone mass due to impaired osteoclast fusion. Expression of dendritic cell-specific transmembrane protein (DC-STAMP), a critical player in osteoclast fusion, was significantly attenuated, and cell fusion of Sbno2-deficient osteoclasts was rescued by DC-STAMP. Sbno2 directly bound to Tal1 and attenuated its inhibition of DC-STAMP expression, leading to activation of the DC-STAMP promoter by MITF. Thus, Sbno2 plays a pivotal role in bone homeostasis in vivo by fine-tuning osteoclast fusion.



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Contact:

Shizuo AKIRA
Host Defense
Immunology Frontier Research Center (WPI-IFReC), Osaka University

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