The association of notch2 and NF-kB accelerates RANKL-induced osteoclastogenesis

Hidefumi Fukushima, Akihiro Nakao, Fujio Okamoto, Masashi Shin, Hiroshi Kajiya, Seiji Sakano, Anna Bigas, Eijiro Jimi, Koji Okabe

研究成果: ジャーナルへの寄稿学術誌査読

139 被引用数 (Scopus)

抄録

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 Jaggedl 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 NFATcl 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.

本文言語英語
ページ(範囲)6402-6412
ページ数11
ジャーナルMolecular and cellular biology
28
20
DOI
出版ステータス出版済み - 10月 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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