Insulin-like growth factor binding Protein-3 suppresses osteoblast differentiation via bone morphogenetic protein-2
Insulin-like growth factor binding Protein-3 suppresses osteoblast differentiation via bone morphogenetic protein-2
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DOI：
10.1016/j.bbrc.2018.11.065
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发表时间：
2018-12-09
影响因子：
3.1
通讯作者：
Uoshima, Katsumi
中科院分区：
文献类型：
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作者：
Eguchi, Kaori;Akiba, Yosuke;Uoshima, Katsumi
在牙种植体中采用了骨强化疗法。虽然诱导骨形成的技术通常是成功的，但维持骨量更为困难。因此，重要的是要了解调控这一过程的机制。胰岛素样生长因子-1(IGF-1)是调节骨量、促进成骨细胞分化、促进骨形成的最丰富的生长因子之一。IGF-1的活性受IGF结合蛋白(IGFBPs)调节。IGFBP-3与IGF-1形成三元络合物，延长其在循环系统中的半衰期。因此，IGFBP-3作为IGF-1的稳定剂和转运体。最近的研究报道了IGFBP-3与骨代谢相关的新的IGF-1非依赖性功能。在本研究中，我们研究了IGFBP-3在成骨细胞分化中的作用。我们的结果表明IGFBP-3降低了成骨细胞分化标志物的表达，而骨形态发生蛋白-2(BMP-2)则促进了成骨细胞分化标志物的表达。IGFBP-3还可降低BMP-2对ALP活性和矿物质结节形成的影响。此外，IGFBP-3还抑制BMP-2信号诱导的Smad结合元件(SBE)报告分子的活性。这些结果提示IGFBP-3通过BMP-2信号通路抑制成骨细胞分化，IGFBP-3可能以IGF-1依赖和非依赖的方式发挥骨量维持作用。(C)2018年作者。由爱思唯尔公司出版。
Bone augmentation therapy is used in dental implantation. While techniques to induce bone formation are generally successful, the maintenance of bone mass is more difficult. Therefore, it is important to understand the mechanisms that regulate this process. Insulin-like growth factor-1 (IGF-1) is one of the most abundant growth factors that regulate bone mass, promote osteoblast differentiation, and accelerate bone formation. The activity of IGF-1 is regulated by IGF-binding proteins (IGFBPs). IGFBP-3 forms a ternary complex with IGF-1, extending its half-life in the circulating system. Therefore, IGFBP-3 acts as a stabilizer and transporter of IGF-1. Recent studies reported new IGF-1-independent functions of IGFBP-3 related with bone metabolism. In this study, we investigated the function of IGFBP-3 in osteoblast differentiation. Our results showed that IGFBP-3 decreases the expression of osteoblast differentiation markers, whose expression is enhanced by bone morphogenetic protein-2 (BMP-2). IGFBP-3 also reduced BMP-2 effect on ALP activity and mineral nodule formation. In addition, IGFBP-3 suppresses the activity of the Smad Binding Element (SBE) reporter, induced by BMP-2 signaling. These results suggest that IGFBP-3 inhibits osteoblast differentiation through the BMP-2 signal pathway, and that IGFBP-3 might play a role in bone mass maintenance in an IGF-1-dependent and -independent manner. (C) 2018 The Authors. Published by Elsevier Inc.