TY - JOUR
T1 - 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
AU - Hirai, Fumihiko
AU - Nakayamada, Shingo
AU - Okada, Yosuke
AU - Saito, Kazuyoshi
AU - Kurose, Hitoshi
AU - Mogami, Akira
AU - Tanaka, Yoshiya
N1 - Funding Information:
We thank Ms. T. Adachi for the excellent technical assistance. This work was supported in part by a Research Grant-in-Aid for Scientific Research by the Ministry of Health, Labor and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan and University of Occupational and Environmental Health, Japan.
PY - 2007/4/27
Y1 - 2007/4/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33947180886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947180886&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.02.121
DO - 10.1016/j.bbrc.2007.02.121
M3 - Article
C2 - 17349971
AN - SCOPUS:33947180886
SN - 0006-291X
VL - 356
SP - 279
EP - 285
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -