Genomewide Molecular and Biologic Characterization of Biomembrane Formation Adjacent to a Methacrylate Spacer in the Rat Femoral Segmental Defect Model
Genomewide Molecular and Biologic Characterization of Biomembrane Formation Adjacent to a Methacrylate Spacer in the Rat Femoral Segmental Defect Model
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DOI：
10.1097/bot.0b013e3182691288
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发表时间：
2013-05-01
影响因子：
2.3
通讯作者：
Kellam, James F.
中科院分区：
文献类型：
--
作者：
Gruber, Helen E.;Gettys, Franklin K.;Kellam, James F.
目的：本研究主要研究骨节段性缺损中围绕甲基丙烯酸酯间隔物形成的细胞层的形态和分子特征。本研究的目的是通过组织学和分子生物学的研究来评价一种新型的啮齿动物股骨节段性缺损模型在术后4、8和16周形成的生物膜。方法：根据机构动物护理和使用委员会的批准，在大鼠股骨制造节段性缺损区并用AO LockingRatNail进行固定，并在术后4、8和16周用数字放射成像、形态和免疫组织化学研究以及全基因组基因表达研究进行分析。结果：甲基丙烯酸酯间隔物周围形成的生物膜富含血管，显示血管内皮生长因子免疫定位。生物膜支持其内部的骨和软骨病灶的形成。骨形态发生蛋白2免疫定位和基因表达在发育中的骨和软骨细胞灶中呈阳性。基因芯片分析显示，与骨和软骨形成及血管生成相关的关键基因显著表达。结论：该大鼠骨模型能有效地构建生物膜。在血管化的生物膜内形成了骨和软骨病灶，并伴随着骨和软骨发育/形成和血管形成关键基因的相关表达。聚甲基丙烯酸甲酯诱导的生物膜为节段性缺陷提供了一种令人兴奋的潜在解决方案；该生物膜既可以作为接受床，也可以作为间充质干细胞的来源，这些干细胞可以被招募/指导修复过程。
Objectives: This study focuses upon the morphologic and molecular features of the layer of cells, termed the "biomembrane," which forms around methacrylate spacers in bone segmental defects. The objective of this research was to assess the biomembrane formed in a novel rodent femoral segmental defect model at 4, 8, and 16 weeks with histologic and molecular studies.Methods: Following Institutional Animal Care and Use Committee approval, a segmental defect was created in the rat femur and stabilized with the AO LockingRatNail and analyzed at 4, 8, and 16 weeks postsurgery using digital radiologic imaging, morphological and immunohistochemical studies, and genomewide gene expression studies employing microarray analysis.Results: The biomembrane formed around the methacrylate spacer was rich in vasculature, which showed vascular endothelial growth factor immunolocalization. The biomembrane supported development of foci of bone and cartilage within it. Bone morphogenetic protein 2 immunolocalization and gene expression were positive within developing osseous and chondrocyte foci. Microarray analysis showed significant expression of key genes related to bone and cartilage formation and angiogenesis.Conclusions: This rat bone model was effective in creation of the biomembrane. Bone and cartilage foci were formed within the vascularized biomembrane with associated expression of genes critical for bone and cartilage development/formation and vascularization. The polymethyl methacrylate-induced biomembrane offers an exciting potential solution for segmental defects; the biomembrane, may act as a receptive bed and also serve as a source for mesenchymal stem cells, which could be recruited/directed for the healing process.