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

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

doi:10.1007/s11010-006-0333-y

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

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

Life Sciences

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	55-61
Number of pages	7
Journal	Molecular and Cellular Biochemistry
Volume	281
Issue number	1-2
DOIs	https://doi.org/10.1007/s11010-006-0333-y
State	Published - Jan 2006

Bibliographical note

Funding Information:
We thank J. Kim for critical reading of the manuscript, G. Bokoch for providing the Rac2 Ab, J. Inoue for provid- ing the pMX-TRAF6 vectors, T. Kitamura for providing the Plat-E cell line and pMXs vectors, E. Eynon for providing the RacN17 vectors, T. Ishitani for providing the TAK1 vectors, and Y. Choi for providing the 3T3 TRAF6−/− cells. This work was supported by Korea Research Foundation Grant (KRF-2000-015-FS0006) (to S.Y.L.).

Keywords

Monocytes
NF-κB
Osteoclast differentiation
Rac1
Signaling cascades

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title = "Rac1 GTPase regulates osteoclast differentiation through TRANCE-induced NF-κB activation",

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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doi = "10.1007/s11010-006-0333-y",

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AU - Lee, Na Kyung

AU - Choi, Han Kyung

AU - Kim, Dong Ku

AU - Lee, Soo Young

N1 - Funding Information: We thank J. Kim for critical reading of the manuscript, G. Bokoch for providing the Rac2 Ab, J. Inoue for provid- ing the pMX-TRAF6 vectors, T. Kitamura for providing the Plat-E cell line and pMXs vectors, E. Eynon for providing the RacN17 vectors, T. Ishitani for providing the TAK1 vectors, and Y. Choi for providing the 3T3 TRAF6−/− cells. This work was supported by Korea Research Foundation Grant (KRF-2000-015-FS0006) (to S.Y.L.).

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N2 - 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.

AB - 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.

KW - Monocytes

KW - NF-κB

KW - Osteoclast differentiation

KW - Rac1

KW - Signaling cascades

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JO - Molecular and Cellular Biochemistry

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IS - 1-2

ER -

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

Abstract

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Keywords

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