IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts
IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts
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DOI：
10.1016/j.bone.2008.07.241
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发表时间：
2008-11-01
期刊：
影响因子：
4.1
通讯作者：
Itoh, Kazuyuki
中科院分区：
文献类型：
--
作者：
Nakasaki, Manando;Yoshioka, Kiyoko;Itoh, Kazuyuki
成骨细胞重新聚集到未来的骨形成部位对于骨骼发育、骨重建和骨折愈合是必不可少的。许多与骨组织相关的因素已被报道诱导成骨细胞定向迁移，但其机制尚不清楚。在本研究中，为了探索成骨细胞的主要趋化因子(S)，我们检测了MC3T3-E1成骨样细胞条件培养液诱导成骨细胞迁移的能力。通过顺序层析和串联质谱分析，我们从条件培养液中纯化并鉴定了IGF-I为一种有效的趋化因子。IGF-I诱导MC3T3-E1细胞和原代小鼠成骨细胞迁移，棋盘分析显示IGF-I显著诱导成骨细胞的定向迁移(趋化)。用单抗中和小鼠IGF-I导致成骨细胞单层伤口愈合延迟和细胞极化，而加入人IGF-I则逆转了这些作用。IGF-I还以整合素β1依赖的方式促进细胞在纤维连接蛋白上的扩散。IGF-I诱导成骨细胞Akt和Rac激活，膜上局部积聚磷脂酰肌醇3，4，5-三磷酸(PtdIns(3，4，5)P(3))。磷脂酰肌醇3激酶(PI3K)抑制剂LY294002可抑制IGF-I诱导的细胞迁移和创面愈合。综上所述，这些结果表明，骨组织中的成骨细胞分泌的IGF-I是一种强大的趋化因子，可能在成骨细胞在骨形成过程中的募集中发挥重要作用。(C)2008 Elsevier Inc.保留所有权利。
Osteoblast recruitment to the site of future done formation is essential for skeletal development, done remodeling and fracture healing. A number of factors associated with bone tissue have been reported to induce directional migration of osteoblasts but the mechanism remains to be clarified. In this Study, to explore a major chemotactic factor(s) for osteoblasts, we examined the serum-free medium conditioned by MC3T3-E1 osteoblast-like cells for its ability to induce osteoblast migration. Employing sequential chromatography and tandem mass spectrometry analysis, we purified and identified IGF-I as a potent chemotactic factor from the conditioned medium. IGF-I induced cell migration of both MC3T3-E1 cells and primary mouse osteoblasts, and checkerboard analysis revealed that IGF-I markedly induced directional migration (chemotaxis) of osteoblasts. Neutralization Of mouse IGF-I with monoclonal antibodies resulted ill delayed osteoblast monolayer wound healing and cellular polarization but addition of human IGF-I reversed these effects. IGF-I also promoted cell spreading on fibronectin in an integrin beta 1-dependent manner. IGF-I induced Akt and Rac activation and localized accumulation of phosphatidylinositol 3,4,5-triphosphate (PtdIns (3,4,5)P(3)) at the membrane in osteoblasts. The phosphatidyl inositol 3 kinase (PI3K) inhibitor LY294002 inhibited IGF-I-induced cell migration and wound healing. Together, the results Suggest that IGF-I secreted from osteoblasts in the bone tissue is a potent chemotactic factor that may play a major role in recruitment of osteoblasts during bone formation. (c) 2008 Elsevier Inc. All rights reserved.