title: Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP.
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.
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors: Kenta
authors: K
authors: Maruyama
authors: Satoshi
authors: S
authors: Uematsu
authors: Takeshi
authors: T
authors: Kondo
authors: Osamu
authors: O
authors: Takeuchi
authors: Mikaël M
authors: MM
authors: Martino
authors: Takumi
authors: T
authors: Kawasaki
authors: Shizuo
authors: S
authors: Akira
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D015726:Giant Cells; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: C499636:DC-STAMP protein, mouse; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C526192:SBNO2 protein, mouse; D051193:Toll-Like Receptors
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