Small GTPase Rho signaling is involved in β1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor κB ligand on osteoblasts and osteoclast maturation

We assessed the characteristics of human osteoblasts, focusing on small GTPase Rho signaling. β1 Integrin were highly expressed on osteoblasts. Engagement of β1 integrins by type I collagen augmented expression of intercellular adhesion molecule 1 (ICAM-1) and receptor activator of nuclear factor κB ligand (RANKL) on osteoblasts. Rho was activated by β1 stimulation in osteoblasts. β1 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 β1 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 β1 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.