Journal of Biological Chemistry
Volume 275, Issue 16, 21 April 2000, Pages 11993-12002
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MECHANISMS OF SIGNAL TRANSDUCTION
Rho-A Is Critical for Osteoclast Podosome Organization, Motility, and Bone Resorption*

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Rho plays a regulatory role in the formation of actin stress fibers and focal adhesions, and it is also involved in integrin-mediated signaling events. To study the role of Rho in αvβ3/gelsolin-dependent signaling, the HIV-Tat peptide, hemagglutinin (HA)-tagged RhoVal-14 (constitutively active) and RhoAsn-19(dominant negative) were transduced into avian osteoclasts. Protein transduction by HA-Tat was highly efficient, and 90–100% of the cells were transduced with HA-tagged proteins. We demonstrate here that RhoVal-14 transduction (100 nm) stimulated gelsolin-associated phosphatidylinositol 3-kinase activity, podosome assembly, stress fiber formation, osteoclast motility, and bone resorption, mimicking osteoclast stimulation by osteopontin/αvβ3. The effects of RhoVal-14 transduction stimulation was time-dependent. C3 exoenzyme blocked the effects of RhoVal-14 and induced podosome disassembly, loss of motility, and inhibition of bone resorption. Transduction of RhoAsn-19 produced podosome disassembly, and blocked osteopontin stimulation. These data demonstrate that integrin-dependent activation of phosphoinositide synthesis, actin stress fiber formation, podosome reorganization for osteoclast motility, and bone resorption require Rho stimulation.

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This work was supported in part by National Institute of Health Grant AR41677 and the Monsanto/Washington University consortium.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.