alexa Integrins, growth factors, and the osteoclast cytoskeleton.


Journal of Cancer Science & Therapy

Author(s): Zou W, Teitelbaum SL

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Abstract The unique ability of the osteoclast to degrade skeletal tissue depends upon formation of a resorptive microenvironment between the osteoclast and the bone surface. Generation of this privileged space is substantially mediated by signals emanating from alphavbeta3 integrin, which transits to its active high-affinity conformation by growth factor-initiated intracellular events targeting the matrix receptor's cytoplasmic domain. The activated liganded integrin stimulates a signaling complex consisting of c-Src, Syk, immunoreceptor tyrosine-based activation motif proteins, Slp-76, Vav3, and members of the Rho family of GTPases. These events contribute to secretory lysososme insertion into the bone-apposed plasma membrane to form the ruffled border that delivers the bone-degrading molecules (HCl and cathepsin K) into the resorptive microenvironment. Integrin/bone recognition also promotes formation of actin rings, which surround the ruffled border, thereby isolating the focus of skeletal degradation from the general extracellular space. This article was published in Ann N Y Acad Sci and referenced in Journal of Cancer Science & Therapy

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