Rac1 GTPase regulates osteoclast differentiation through TRANCE-induced NF-κB activation

Na Kyung Lee, Han Kyung Choi, Dong Ku Kim, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Signaling by tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) is essential for the differentiation of monocytes/ macrophages into osteoclasts. We show here that TRANCE selectively activates Rac1, but not Rac2 in osteoclast precursors. Expression of a dominant interfering mutant of TNF receptor-associated factor (TRAF)6 blocks TRANCE-mediated Rac1 activation, indicating that Rac1 lies downstream of TRAF6. Osteoclast precursors expressing a dominant negative Rac1N17 are defective in TRANCE-induced IKK activation and IκBα degradation resulting in inhibition of NFκB-dependent reporter gene activity. In addition, Rac1 acts upstream of TAK1 to induce NF-κB activation and is required for the normal differentiation of osteoclast precursors. Thus, Rac1 may represent a key regulator for differentiation of osteoclasts through the activation of NF-κB.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume281
Issue number1-2
DOIs
StatePublished - Jan 2006

Keywords

  • Monocytes
  • NF-κB
  • Osteoclast differentiation
  • Rac1
  • Signaling cascades

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