The association of Notch2 and NF-kappaB accelerates RANKL-induced osteoclastogenesis |
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Authors: | Fukushima Hidefumi Nakao Akihiro Okamoto Fujio Shin Masashi Kajiya Hiroshi Sakano Seiji Bigas Anna Jimi Eijiro Okabe Koji |
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Institution: | Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, Japan. r07fukushima@fa.kyu-dent.ac.jp |
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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 γ-secretase inhibitor or Notch2 short hairpin RNA 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 nuclei of RANKL-stimulated cells and that both proteins are recruited to the NFATc1 promoter, driving its expression. Taken together, our results show a new molecular cross talk between Notch and NF-κB pathways that is relevant in osteoclastogenesis. |
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