Small GTPase Rho signaling is involved in beta 1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor kappa B ligand on osteoblasts and osteoclast maturation

摘要

We assessed the characteristics of human osteoblasts, focusing on small GTPase Rho signaling. beta 1 Integrin were highly expressed on osteoblasts. Engagement of beta 1 integrins by type I collagen augmented expression of intercellular adhesion molecule I (ICAM-1) and receptor activator of nuclear factor kappa beta ligand (RANKL) on osteoblasts. Rho was activated by beta 1 stimulation in osteoblasts. beta 1 Integrin-induced up-regulation of ICAM-1 and RANKL was inhibited by transfection with adenoviruses encoding C3 transferase or pretreated with Y-27632, specific Rho and Rho-kinase inhibitors. Engagement of beta 1 integrin on osteoblasts induced formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNC) in a coculture system of osteoblasts and peripheral monocytes. but this action was completely abrogated by transfection of C3 transferase. Our results indicate the direct involvement of Rho-mediated signaling in beta 1 integrin-induced up-regulation of ICAM-1 and RANKL and RANKL-dependent osteoclast maturation. Thus, Rho-mediated signaling in osteoblasts seems to introduce major biases to bone resorption. (c) 2007 Elsevier Inc. All rights reserved.