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

Research output: Contribution to journalArticlepeer-review

150 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)6402-6412
Number of pages11
JournalMolecular and cellular biology
Issue number20
Publication statusPublished - Oct 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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