title: Small GTPase Rho signaling is involved in beta1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor kappaB ligand on osteoblasts and osteoclast maturation.
abstract: We assessed the characteristics of human osteoblasts, focusing on small GTPase Rho signaling. Beta1 Integrin were highly expressed on osteoblasts. Engagement of beta1 integrins by type I collagen augmented expression of intercellular adhesion molecule 1 (ICAM-1) and receptor activator of nuclear factor kappaB ligand (RANKL) on osteoblasts. Rho was activated by beta1 stimulation in osteoblasts. Beta1 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 beta1 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 beta1 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.
authors.affiliation: First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hirai
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakayamada
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okada
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurose
authors.forename: Akira
authors.initials: A
authors.lastname: Mogami
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D001905:Botulinum Toxins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000071681:Tartrate-Resistant Acid Phosphatase; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000577:Amides; D024042:Collagen Type I; D004791:Enzyme Inhibitors; D019012:Integrin beta1; D007527:Isoenzymes; D011725:Pyridines; D053245:RANK Ligand; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C108830:Y 27632; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins