Local application of rhTGF-beta2 modulates dynamic gene expression in a rat implant model.
Local application of rhTGF-beta2 modulates dynamic gene expression in a rat implant model.
复制标题
rhTGF-β2 的局部应用调节大鼠植入模型中的动态基因表达。
DOI：
10.1016/j.bone.2005.01.019
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Sumner,DaleR
中科院分区：
文献类型：
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作者：
DeRanieri,Aladino;Virdi,AmarjitS;Kuroda,Shinji;Shott,Susan;Dai,Yang;Sumner,DaleR
多种合成代谢药物，包括转化生长因子-β(转化生长因子-β)，已被证明可以促进膜内骨再生和加强种植体与宿主骨骼之间的机械连接，这是骨科和牙科种植体临床成功的先决条件。在基因水平上的这些观察结果背后的机制几乎没有受到关注。用实时定量聚合酶链式反应检测大鼠种植体植入后1、3、5、7、10、14、28天的21个“成骨”基因的转录水平。对照组和1μg重组人转化生长因子-转化生长因子-β2处理组(n=42，平均分为2组和7个时间点)。选择的基因代表三个功能类别：(1)生长因子及其受体和拮抗剂；(2)骨分化标记物；(3)炎症标记物。对转录图谱的检测表明，9个基因的表达水平上调或下调，时间没有变化，12个基因的表达谱加速或延迟，同时或不伴随最高或最低表达的变化。最早的变化(第1-3天)涉及胰岛素样生长因子-1R和血管内皮生长因子的表达加速，以及转化生长因子-β-2、T-βRI、骨形态发生蛋白-2、骨形态发生蛋白-7和Cbfa1的上调。此外，主成分分析表明，尽管在生长因子治疗后这些亚集的时间关系发生了变化，但这些基因的某些亚集在两组中都是共表达的。因此，除了个体转录谱的变化外，在骨再生过程中，共表达基因之间的调控连接也可能受到外源性合成代谢药物的影响。
Various anabolic agents, including transforming growth factor-beta (TGF-β), have been shown to enhance intramembranous bone regeneration and strengthen the mechanical connection between implant and host skeleton, a prerequisite for clinical success with orthopedic and dental implants. Mechanisms underlying these observations at the level of the gene have received little attention. A rat model was used to examine levels of gene transcription for 21 “osteogenic” genes by real-time polymerase chain reaction at days 1, 3, 5, 7, 10, 14, and 28 in a control group and a group in which the implant was treated with 1 μg recombinant human TGF-β2 (n = 42, equally divided among the 2 groups and 7 time points). Genes were chosen to represent three functional categories: (1) growth factors, their receptors and antagonists; (2) bone differentiation markers; and (3) inflammation markers. Examination of the transcription profiles showed that nine genes had up-regulated or down-regulated expression levels without a change in timing and 12 genes had accelerated or delayed expression profiles with or without a concomitant change in maximal or minimal expression. The earliest changes (days 1–3) involved accelerated expression profiles for IGF-1R and VEGF and up-regulation of TGF-β2, TβRI, BMP-2, BMP-7, and Cbfa1. Furthermore, principal components analyses showed that some subsets of genes were co-expressed in both groups, although the temporal relationship of these subsets was altered following growth factor treatment. Thus, in addition to changes in individual transcription profiles, the regulatory connections between sets of co-expressed genes may also be affected by exogenously delivered anabolic agents during bone regeneration.