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Mol. Cell. Biol. doi:10.1128/MCB.00299-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The association of Notch2 and NF-B accelerates RANKL-induced osteoclastogenesis

Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, Japan; Department of Bioscience, and Center for Oral Biological Research, Kyushu Dental College, Kitakyushu 803-8580, Japan; Central R&D Laboratories, Asahi Kasei Corporation, Shizuoka 416-8501 Japan; Molecular Oncology, IDIBELL, Hospitalet-Barcelona 08907, Spain

^* To whom correspondence should be addressed. Email: r07fukushima{at}fa.kyu-dent.ac.jp.

	Abstract

Notch signaling plays a key role in various cell differentiation processes including bone homeostasis. However, the specific involvement of Notch in regulating osteoclastogenesis is still controversial. In the present study, we show that RANKL induces expression of Jagged1 and Notch2 in bone marrow macrophages during osteoclast differentiation. Suppression of Notch signaling by a selective -secretase inhibitor or Notch2 shRNA suppresses RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by Jagged1, or by ectopic expression of intracellular Notch2, enhances NFATc1 promoter activity and expression and promotes osteoclastogenesis. Finally, we found that Notch2 and p65 interact in the nucleus of RANKL-stimulated cells and both proteins are recruited to the NFATc1 promoter driving its expression. Taken together, our results show a new molecular crosstalk between Notch and NF-B pathways that is relevant in osteoclastogenesis.