Coordinated regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by endogenous bone morphogenetic proteins.
Coordinated regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by endogenous bone morphogenetic proteins.
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DOI：
10.1016/j.bone.2014.12.057
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发表时间：
2015-04
期刊：
影响因子：
4.1
通讯作者：
Boyan, Barbara D.
中科院分区：
文献类型：
--
作者：
Olivares-Navarrete, Rene;Hyzy, Sharon L.;Haithcock, David A.;Cundiff, Caitlin A.;Schwartz, Zvi;Boyan, Barbara D.
人骨髓间充质干细胞（MSC）分化成成骨细胞的微结构钛（Ti）表面上没有添加培养基补充剂，表明表面依赖的内源性机制参与。它们产生骨形态发生蛋白（BMP），通过BMP mRNA和蛋白质、受体和抑制剂（Noggin、Cerberus、Gremlin 1和Chordin）变化调节的自分泌/旁分泌机制调节MSC分化和骨形成。我们研究了BMP及其受体和抑制剂随时间的表达，并使用BMP 2沉默细胞来确定调节内源性BMP信号传导如何影响该过程。将MSC在组织培养聚苯乙烯或Ti [PT（Ra<0.4μm）;喷砂/酸蚀刻Ti（SLA，Ra=3.2μm）;或结晶-SLA（modSLA）]上培养。BMP mRNA和蛋白质在培养第4天增加。外源性BMP 2增加了分化，而BMP 2沉默的细胞中分化降低。Noggin在第2天受到调节，而Gremlin 1和Cerberus在6天后受到调节。成骨细胞分化增加的细胞培养的阻断抗体头蛋白，Gremlin 1，和地狱犬。内源性BMP增强成骨微环境，而外源性BMP是抑制性的。BMP 2抑制剂Cerberus的抗体阻断导致IL-6和IL-8水平与用外源性BMP 2处理细胞时观察到的水平相似，而靶向抑制剂Gremlin或Noggin的抗体则没有。这些结果表明，支持治疗性干细胞的微结构钛植入物可以用适当选择的拮抗细胞外BMP抑制剂的试剂进行处理，以增强BMP 2介导的骨修复，同时避免外源性BMP 2治疗观察到的不良炎症副作用。
Human mesenchymal stem cells (MSCs) differentiate into osteoblasts on microstructured titanium (Ti) surfaces without addition of medium supplements, suggesting that surface-dependent endogenous mechanisms are involved. They produce bone morphogenetic proteins (BMPs), which regulate MSC differentiation and bone formation via autocrine/paracrine mechanisms that are modulated by changes in BMP mRNA and protein, receptors, and inhibitors (Noggin, Cerberus, Gremlin 1, and Chordin). We examined expression of BMPs, their receptors and their inhibitors over time and used BMP2-silenced cells to determine how modulating endogenous BMP signaling can affect the process. MSCs were cultured on tissue culture polystyrene or Ti [PT (Ra<0.4μm); sandblasted/acid-etched Ti (SLA, Ra=3.2μm); or hydrophilic-SLA (modSLA)]. BMP mRNAs and proteins increased by day 4 of culture. Exogenous BMP2 increased differentiation whereas differentiation was decreased in BMP2-silenced cells. Noggin was regulated by day 2 whereas Gremlin 1 and Cerberus were regulated after 6 days. Osteoblastic differentiation increased in cells cultured with blocking antibodies against Noggin, Gremlin 1, and Cerberus. Endogenous BMPs enhance an osteogenic microenvironment whereas exogenous BMPs are inhibitory. Antibody blocking of the BMP2 inhibitor Cerberus resulted in IL-6 and IL-8 levels that were similar to those observed when treating cells with exogenous BMP2, while antibodies targeting the inhibitors Gremlin or Noggin did not. These results suggest that microstructured titanium implants supporting therapeutic stem cells may be treated with appropriately selected agents antagonistic to extracellular BMP inhibitors in order to enhance BMP2 mediated bone repair while avoiding undesirable inflammatory side effects observed with exogenous BMP2 treatment.
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影响因子：
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作者：
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影响因子：
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影响因子：
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