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.
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.
Hirai
Fumihiko
F
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan.
Nakayamada
Shingo
S
Okada
Yosuke
Y
Saito
Kazuyoshi
K
Kurose
Hitoshi
H
Mogami
Akira
A
Tanaka
Yoshiya
Y
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*
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