Overexpression of insulin-like growth factor binding protein-5 decreases osteoblastic function in vitro
Overexpression of insulin-like growth factor binding protein-5 decreases osteoblastic function in vitro
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DOI：
10.1016/j.bone.2004.08.011
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发表时间：
2004-12-01
期刊：
影响因子：
4.1
通讯作者：
Canalis, E
中科院分区：
文献类型：
--
作者：
Durant, D;Pereira, RMR;Canalis, E
骨骼细胞合成胰岛素样生长因子（IGF）及其结合蛋白（IGFBP）。IGFBP-5对骨细胞生长和成骨功能的影响存在争议，过表达IGFBP-5的转基因小鼠表现出骨减少。其机制尚未探讨，在本研究中，我们在体外研究了IGFBP-5过表达对MC3T3细胞的影响。MC3T3细胞被逆转录病毒载体（pLPCX）或在组成型启动子控制下引导IGFBP-5转录的载体转导。未处理的MC3T3细胞在融合1周后表达碱性磷酸酶和骨钙素mRNA，培养4周时形成矿化结节。IGFBP-5过表达延迟了碱性磷酸酶和骨钙素mRNA的出现，降低了I型胶原和骨桥蛋白mRNA和碱性磷酸酶活性（APA），抑制了矿化结节的形成。IGFBP-5引起了DNA合成的适度刺激。综上所述，IGFBP-5过表达可能通过与骨微环境中的IGFs结合而降低成骨细胞功能。(C) 2004爱思唯尔公司版权所有。
Skeletal cells synthesize insulin-like growth factors (IGF) and their binding proteins (IGFBP). The effects of IGFBP-5 on bone cell growth and osteoblastic function are controversial, and transgenic mice overexpressing IGFBP-5 exhibit osteopenia. The mechanisms were not explored, and in this study, we investigated the effects of IGFBP-5 overexpression in MC3T3 cells in vitro. MC3T3 cells were transduced with a retroviral vector (pLPCX) or a vector directing IGFBP-5 transcription under the control of a constitutive promoter. Untreated MC3T3 cells expressed alkaline phosphatase, and osteocalcin mRNA I week after confluence and at 4 weeks of culture they formed mineralized nodules. IGFBP-5 overexpression delayed the appearance of alkaline phosphatase and osteocalcin mRNA, decreased type I collagen and osteopontin mRNA and alkaline phosphatase activity (APA), and inhibited the formation of mineralized nodules. IGFBP-5 caused a modest stimulation of DNA synthesis. In conclusion, overexpression of IGFBP-5 decreases osteoblastic function possibly by binding IGFs in the bone microenvironment. (C) 2004 Elsevier Inc. All rights reserved.