Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells.
Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells.
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DOI：
10.1186/ar2436
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发表时间：
2008
影响因子：
4.9
通讯作者：
Evans CH
中科院分区：
文献类型：
--
作者：
Kwong FN;Richardson SM;Evans CH
骨形态发生蛋白（BMP）是胚胎发育和成人骨折修复过程中祖细胞成骨分化的关键生长因子。虽然重组骨形成蛋白已在临床上使用，但其临床效率有待提高。骨形成蛋白的生物学活性受细胞外结合蛋白的天然调节。在这项研究中测试的具体假设如下：BMP抑制剂chordin是内源性的人骨髓间充质干细胞（MSCs）的成骨分化过程中产生的;和BMP抑制剂的活性的阻断增加人MSCs在体外的成骨分化的速率。人MSC来源于来自髂嵴抽吸物和来自经历髋关节半置换术的患者的骨髓。使用标准成骨分化培养基沿成骨途径诱导MSC，并通过基因表达分析测定BMP-2和脊索蛋白的表达。在成骨分化过程中，使用RNA干扰诱导脊索蛋白敲低。成骨分化通过测量碱性磷酸酶的表达和钙沉积来评估。各组间成骨标志物表达差异用方差分析比较，然后用Gabriel事后检验。我们证明了BMP-2和chordin在人MSCs成骨分化过程中的表达。在体外通过RNA干扰敲低脊索蛋白导致成骨标志物碱性磷酸酶的表达和细胞外矿物质的沉积显著增加，以响应成骨刺激。我们的结论是，内源性产生的腱蛋白抑制人骨髓间充质干细胞的成骨分化。靶向BMP抑制剂，如chordin，可能为促进骨再生提供一种新的策略。
Bone morphogenetic proteins (BMPs) are critical growth factors in the osteogenic differentiation of progenitor cells during development in embryos and fracture repair in adults. Although recombinant BMPs are in use clinically, their clinical efficiency needs to be improved. The biological activities of BMPs are naturally regulated by extracellular binding proteins. The specific hypotheses tested in this study were as follows: the BMP inhibitor chordin is produced endogenously during the osteogenic differentiation of human mesenchymal stem cells (MSCs); and blockade of the activity of the BMP inhibitor increases the rate of osteogenic differentiation of human MSCs in vitro. Human MSCs were derived from bone marrow from an iliac crest aspirate and from patients undergoing hip hemiarthroplasty. The MSCs were induced down the osteogenic pathway using standard osteogenic differentiation media, and expressions of BMP-2 and chordin were determined by gene expression analysis. During osteogenic differentiation, chordin knockdown was induced using RNA interference. Osteogenic differentiation was assessed by measuring the expression of alkaline phosphatase and calcium deposition. The differences in expression of osteogenic makers between groups were compared by analysis of variance, followed by Gabriel post hoc test. We demonstrate the expression of BMP-2 and chordin in human MSCs during osteogenic differentiation. Knockdown of chordin by RNA interference in vitro resulted in a significant increase in the expression of the osteogenic marker alkaline phosphatase and the deposition of extracellular mineral, in response to osteogenic stimulation. We conclude that endogenously produced chordin constrains the osteogenic differentiation of human MSCs. The targeting of BMP inhibitors, such as chordin, may provide a novel strategy for enhancing bone regeneration.
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影响因子：
4.1
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