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J Exp Med. 2013 Sep 23;210(10):1947-60. doi: 10.1084/jem.20130512. Epub 2013 Aug 26.

Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP.

Author information

1
Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.

Abstract

Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). We 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-κB repression. However, the role of Sbno2 in vivo and its pleiotropic functions are unknown. Sbno2 gene targeting resulted in normal NF-κB 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 T cell acute lymphocytic leukemia 1 (Tal1) and attenuated its inhibition of DC-STAMP expression, leading to activation of the DC-STAMP promoter by microphthalmia-associated transcription factor (MITF). Thus, Sbno2 plays a pivotal role in bone homeostasis in vivo by fine-tuning osteoclast fusion.

PMID:
23980096
PMCID:
PMC3782043
DOI:
10.1084/jem.20130512
[Indexed for MEDLINE]
Free PMC Article
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