| First Author | Maruyama K | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 10 | Pages | 1947-60 |
| PubMed ID | 23980096 | Mgi Jnum | J:202853 |
| Mgi Id | MGI:5522615 | Doi | 10.1084/jem.20130512 |
| Citation | Maruyama K, et al. (2013) Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP. J Exp Med 210(10):1947-60 |
| abstractText | Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of nuclear factor kappaB (NF-kappaB) 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-kappaB repression. However, the role of Sbno2 in vivo and its pleiotropic functions are unknown. Sbno2 gene targeting resulted in normal NF-kappaB 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. |
