Differential Effects of Bone Morphogenetic Protein-2 and Transforming Growth Factor-β1 on Gene Expression of Collagen-Modifying Enzymes in Human Adipose Tissue-Derived Mesenchymal Stem Cells
Differential Effects of Bone Morphogenetic Protein-2 and Transforming Growth Factor-β1 on Gene Expression of Collagen-Modifying Enzymes in Human Adipose Tissue-Derived Mesenchymal Stem Cells
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DOI：
10.1089/ten.tea.2007.0184
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发表时间：
2009-08-01
影响因子：
4.1
通讯作者：
Klein-Nulend, Jenneke
中科院分区：
文献类型：
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作者：
Knippenberg, Marlene;Helder, Marco N.;Klein-Nulend, Jenneke
脂肪组织来源的间充质干细胞 (AT-MSC) 与骨形态发生蛋白 2 (BMP-2) 或转化生长因子 β 1 (TGF-β 1) 相结合，用于骨组织工程的评估正在进行中。 I 型胶原蛋白的翻译后修饰对于具有足够物理和机械性能的功能性骨组织至关重要。我们研究了 BMP-2 (10-100 ng/mL) 和/或 TGF-β 1 (1-10 ng/mL) 是否影响人 AT-MSC 的 α2(I) 前胶原和胶原修饰酶（即赖氨酰氧化酶和赖氨酰羟化酶 1、2 和 3（由 PLOD1、2 和 3 编码））的基因表达。 28 天后，BMP-2（而非 TGF-b beta 1）增加碱性磷酸酶活性，表明 AT-MSC 的成骨分化。第 4 天时，BMP-2 和 TGF-β 1 均上调 α 2(I) 前胶原和 PLOD1，后者在第 28 天下调。第 28 天时，TGF-β 1 而不是 BMP-2 下调 PLOD3。赖氨酰氧化酶在第 4 天被 TGF-β 1 上调，在第 7 天被 BMP-2 上调。BMP-2 和 TGF-β 1 均不受影响PLOD2。总之，这些结果表明 AT-MSC 对 BMP-2 和 TGF-β 1 的反应存在差异，且胶原修饰酶基因表达发生变化。因此，AT-MSC 可能能够适当修饰 I 型胶原蛋白，形成用于组织工程的功能性骨细胞外基质，具体取决于添加的生长因子。
Adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-beta 1 (TGF-beta 1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We investigated whether BMP-2 (10-100 ng/mL) and/or TGF-beta 1 (1-10 ng/mL) affect gene expression of alpha 2(I) procollagen and collagen-modifying enzymes, that is, lysyl oxidase and lysyl hydroxylases 1, 2, and 3 (encoded by PLOD1, 2, and 3), by human AT-MSCs. BMP-2, but not TGF-b beta 1, increased alkaline phosphatase activity after 28 days, indicating osteogenic differentiation of AT-MSCs. At day 4, both BMP-2 and TGF-beta 1 upregulated alpha 2(I) procollagen and PLOD1, which was downregulated at day 28. TGF-beta 1, but not BMP-2, downregulated PLOD3 at day 28. Lysyl oxidase was upregulated by TGF-beta 1 at day 4 and by BMP-2 at day 7. Neither BMP-2 nor TGF-beta 1 affected PLOD2. In conclusion, these results suggest that AT-MSCs differentially respond to BMP-2 and TGF-beta 1 with changes in gene expression of collagen-modifying enzymes. AT-MSCs may thus be able to appropriately modify type I collagen to form a functional bone extracellular matrix for tissue engineering, dependent on the growth factor added.