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
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
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DOI：
10.1016/j.bbrc.2007.02.121
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发表时间：
2007-04-27
影响因子：
3.1
通讯作者：
Tanaka, Yoshiya
中科院分区：
文献类型：
--
作者：
Hirai, Fumihiko;Nakayamada, Shingo;Tanaka, Yoshiya
我们评估了人类成骨细胞的特征，重点关注小 GTPase Rho 信号传导。 β1整合素在成骨细胞上高表达。 I 型胶原蛋白与 β1 整合素的结合增强了成骨细胞上细胞间粘附分子 I (ICAM-1) 和核因子 κβ 配体受体激活剂 (RANKL) 的表达。 Rho 被成骨细胞中的 β1 刺激激活。 β1 整合素诱导的 ICAM-1 和 RANKL 上调可通过编码 C3 转移酶的腺病毒转染或用特异性 Rho 和 Rho 激酶抑制剂 Y-27632 预处理来抑制。在成骨细胞和外周单核细胞的共培养系统中，β1 整合素与成骨细胞的结合诱导了抗酒石酸酸性磷酸酶 (TRAP) 阳性多核细胞 (MNC) 的形成。但这种作用被C3转移酶的转染完全消除。我们的结果表明，Rho 介导的信号直接参与 β1 整合素诱导的 ICAM-1 和 RANKL 上调以及 RANKL 依赖性破骨细胞成熟。因此，成骨细胞中 Rho 介导的信号传导似乎对骨吸收产生了重大偏差。 (c) 2007 Elsevier Inc. 保留所有权利。
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.