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.
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Lee, N.K., Choi, H.K., Kim, DK. et al. Rac1 GTPase regulates osteoclast differentiation through TRANCE-induced NF-κB activation. Mol Cell Biochem 281, 55–61 (2006). https://doi.org/10.1007/s11010-006-0333-y
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DOI: https://doi.org/10.1007/s11010-006-0333-y