Mechanisms regulating increased production of osteoprotegerin by osteoblasts cultured on microstructured titanium surfaces.
Mechanisms regulating increased production of osteoprotegerin by osteoblasts cultured on microstructured titanium surfaces.
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DOI：
10.1016/j.biomaterials.2009.03.047
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发表时间：
2009-07
期刊：
影响因子：
14
通讯作者：
Boyan, Barbara D.
中科院分区：
文献类型：
--
作者：
Schwartz, Zvi;Olivares-Navarrete, Rene;Wieland, Marco;Cochran, David L.;Boyan, Barbara D.
生长在微结构钛表面的成骨细胞通过产生调节骨形成和骨重建的局部因子来促进骨整合，包括RANK配体诱骗受体骨保护素(OPG)。本研究的目的是探讨表面微结构和表面能对OPG表达的刺激作用机制。制备的钛圆盘呈现不同的表面形态：光滑的前处理表面(Pt，Ra<；0.2μm)、微结构喷砂/酸蚀表面(Sla，Ra=3-4μm)和微结构钛等离子喷涂表面(Tps，Ra=4μm)。培养人成骨样MG63细胞，检测转化生长因子-β-1、蛋白激酶C和α-2-β-1整合素信号对成骨细胞生成的调节作用。成骨细胞在SLA和TPS上生长时，产生大量的成骨细胞以及活性和潜伏性的转化生长因子-β-1，并具有较高的蛋白激酶C活性。外源性转化生长因子-β-1以剂量依赖的方式增加所有表面的骨形态发生蛋白的产生，这可以通过增加转化生长因子-βII型受体的封闭抗体或通过加入外源性可溶性的II型受体来减少转化生长因子-β1与受体的结合而被阻止。PKC抑制剂白屈菜红碱以剂量依赖的方式抑制OPG的产生，但仅在SLA和TPS上。α2的shRNA敲除或α2β1的双重敲除也可减少成骨细胞的成骨细胞生长因子和转化生长因子β1的产生。这些结果表明，底物依赖的成骨细胞生长因子的产生受转化生长因子β1、蛋白激酶C和α2β1的调节，提示了α2β1信号增加蛋白激酶C的机制，从而导致转化生长因子2β1的产生，转化生长因子β1作用于其受体从而增加成骨细胞生长因子的转录。
Osteoblasts grown on microstructured Ti surfaces enhance osteointegration by producing local factors that regulate bone formation as well as bone remodeling, including the RANK ligand decoy receptor osteoprotegerin (OPG). The objective of this study was to explore the mechanism by which surface microstructure and surface energy mediate their stimulatory effects on OPG expression. Titanium disks were manufactured to present different surface morphologies: a smooth pretreatment surface (PT, Ra<0.2μm), microstructured sandblasted/acid etched surface (SLA, Ra=3-4μm), and a microstructured Ti plasma-sprayed surface (TPS, Ra=4μm). Human osteoblast-like MG63 cells were cultured on these substrates and the regulation of OPG production by TGF-β1, PKC, and α2β1 integrin signaling determined. Osteoblasts produced increased amounts of OPG as well as active and latent TGF-β1 and had increased PKC activity when grown on SLA and TPS. Exogenous TGF-β1 increased OPG production in a dose-dependent manner on all surfaces, and this was prevented by adding blocking antibody to the TGF-β type II receptor or by reducing TGF-β1 binding to the receptor by adding exogenous soluble type II receptor. The PKC inhibitor chelerythrine inhibited the production of OPG in a dose-dependent manner, but only in cultures on SLA and TPS. shRNA knockdown of α2 or a double knockdown of α2β1 also reduced OPG, as well as production of TGF-β1. These results indicate that substrate dependent OPG production is regulated by TGF-β1, PKC, and α2β1 and suggest a mechanism by which α2β1-signaling increases PKC, resulting in TGF-β1 production and TGF-β1 then acts on its receptor to increase transcription of OPG.
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