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 language | English |
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Pages (from-to) | 55-61 |
Number of pages | 7 |
Journal | Molecular and Cellular Biochemistry |
Volume | 281 |
Issue number | 1-2 |
DOIs | |
State | Published - Jan 2006 |
Keywords
- Monocytes
- NF-κB
- Osteoclast differentiation
- Rac1
- Signaling cascades