Strawberry Notch Homologue 2 Regulates Osteoclast Fusion by Enhancing the Expression of DC-STAMP

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2013 Aug 28

PMID 23980096

Citations 32

Authors

Kenta Maruyama

Satoshi Uematsu

Takeshi Kondo

Osamu Takeuchi

Mikael M Martino

Takumi Kawasaki

Shizuo Akira

Affiliations

Soon will be listed here.

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.

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