Bone Morphogenetic Protein 2 Alters Osteogenesis and Anti-Inflammatory Profiles of Mesenchymal Stem Cells Induced by Microtextured Titanium In Vitro
Bone Morphogenetic Protein 2 Alters Osteogenesis and Anti-Inflammatory Profiles of Mesenchymal Stem Cells Induced by Microtextured Titanium In Vitro
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DOI：
10.1089/ten.tea.2017.0003
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发表时间：
2017-10-01
影响因子：
4.1
通讯作者：
Schwartz, Zvi
中科院分区：
文献类型：
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作者：
Hyzy, Sharon L.;Olivares-Navarrete, Rene;Schwartz, Zvi
目的：微织构钛在无外源性成骨因子的情况下诱导间充质干细胞向成骨细胞分化，高能表面修饰可加速微细钛种植体的愈合。骨形态发生蛋白2(BMP2)在临床上用于改善种植体周围骨形成和骨整合，但会引起炎症和骨相关并发症。材料和方法：将人骨髓间充质干细胞培养在钛基质(光滑[PT]、喷砂酸蚀[SLA]、亲水性SLA[modSLA])或组织培养聚苯乙烯(TCPS)上。7d后，用聚合酶链式反应阵列检测炎性细胞的mRNAs。此外，对培养7天的细胞用外源性BMP2和成骨分化及产生局部因子、促炎因子和抗炎因子进行评估。结果：细胞因子、趋化因子、细胞因子和生长因子的表达受表面性质的影响，尤以modSLA为甚。钛上的MSCs比TCPS上的细胞产生更少的吸收因子和更多的成骨/抗炎因子。加入100 ng/mLBMP2不仅促进分化，而且增加促炎作用，减少抗炎/抗吸收因子。每毫升200毫微克的BMP2阻止了成骨，并显著增加了促破骨因子。在BMP2-DIP涂层的圆盘上培养的MSCs表现出相似的促炎性特征，并抑制成骨分化，并在最高剂量下增加了凋亡标记物。结论：MSCs在微结构钛表面进行了成骨并调节了炎症细胞因子。外源性BMP2抑制了MSC的分化，并刺激了剂量依赖的促炎和凋亡反应。BMP2与微纹理金属种植体一起使用可能会增加炎症，并可能延迟骨形成，这取决于剂量，这表明在种植体植入期间临床应用BMP2可能需要重新评估。
Objectives: Microtextured titanium (Ti) induces osteoblast differentiation of mesenchymal stem cells (MSCs) in the absence of exogenous osteogenic factors; and high-energy surface modifications speed healing of microrough Ti implants. Bone morphogenetic protein 2 (BMP2) is used clinically to improve peri-implant bone formation and osseointegration but can cause inflammation and bone-related complications. In this study, we determined whether BMP2 alters human MSC differentiation, apoptosis, and inflammatory factor production when grown on Ti implants with different surface properties.Materials and Methods: Human MSCs were cultured on Ti substrates (smooth [PT], sandblasted acid-etched [SLA], hydrophilic-SLA [modSLA]), or tissue culture polystyrene (TCPS). After 7 days, inflammatory mRNAs were measured by polymerase chain reaction array. In addition, 7-day cultures were treated with exogenous BMP2 and osteogenic differentiation and production of local factors, proinflammatory interleukins, and anti-inflammatory interleukins assessed. Finally, osteogenic markers and interleukins were measured in MSCs cultured for 48 h on BMP2 dip-coated SLA and modSLA surfaces.Results: Expression of interleukins, chemokines, cytokines, and growth factors was affected by surface properties, particularly on modSLA. MSCs on Ti produced fewer resorptive and more osteogenic/anti-inflammatory factors than cells on TCPS. Addition of 100 ng/mL BMP2 not only increased differentiation but also increased proinflammatory and decreased anti-inflammatory/antiresorptive factors. Two hundred nanograms per milliliter BMP2 abolished osteogenesis and dramatically increased pro-osteoclastogenic factors. MSCs cultured on BMP2-dip-coated disks produced similar proinflammatory profiles with inhibited osteogenic differentiation and had increased apoptotic markers at the highest doses.Conclusions: MSCs underwent osteogenesis and regulated inflammatory cytokines on microtextured Ti. Exogenous BMP2 inhibited MSC differentiation and stimulated a dose-dependent proinflammatory and apoptotic response. Use of BMP2 with microtextured metal implants may increase inflammation and possibly delay bone formation dependent on dose, suggesting that application of BMP2 clinically during implant insertion may need to be reevaluated.