TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.
TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.
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DOI：
10.1371/journal.pone.0053086
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hunziker EB
中科院分区：
文献类型：
--
作者：
Shintani N;Siebenrock KA;Hunziker EB
滑膜组织移植为关节软骨的修复提供了原位间充质干细胞群。虽然骨形态发生蛋白2（BMP-2）诱导牛滑膜外植体的软骨形成，但形成的软骨既不是均匀分布的，也不是完全透明的类型。此外，软骨细胞的下游分化进行到终末肥大阶段，这与不希望的基质矿化不可避免地结合在一起。为了优化BMP-2诱导的软骨形成，研究了成纤维细胞生长因子2（FGF-2）和转化生长因子β 1（TGF-β 1）的调节作用。将小牛掌骨滑膜的外植体暴露于BMP-2（200 ng/ml）4（或6）周。FGF-2（10 ng/ml）或TGF-β 1（10 ng/ml）在孵育开始时引入，并在单独培养的第一周或整个培养过程中存在。FGF-2仅在单独培养的第一周期间存在时增强BMP-2诱导的糖胺聚糖（GAG）异染染色的增加。当TGF-β 1存在于整个培养期间时，它不仅增强了BMP-2诱导的异染性增加（比FGF-2更大程度），而且增强了生物化学测定的GAG积累;此外，它在肥大的早期阶段阻止了细胞的下游分化。这些发现得到了关键软骨标志物的基因和蛋白质表达水平分析以及单个细胞体积估计的证实。TGF-β 1增强牛滑膜外植体的BMP-2诱导的软骨形成，改善新软骨的透明样性质，并在肥大的早期阶段阻止细胞的下游分化。随着工程的成熟，真正的关节型软骨在临床修复的背景下的前景，我们的研究结果将是重要的微调刺激方案的最佳软骨分化的滑膜外植体。
Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2) induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2) and transforming growth factor beta 1 (TGF-ß1) were investigated. Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml) for 4 (or 6) weeks. FGF-2 (10 ng/ml) or TGF-ß1 (10 ng/ml) was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs) only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2), but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of clinical repair, our findings will be of importance in fine-tuning the stimulation protocol for the optimal chondrogenic differentiation of synovial explants.
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DOI：
10.1016/j.bbrc.2006.02.171
发表时间：
2006-05-05
影响因子：
3.1
作者：
Chiou, M;Xu, Y;Longaker, MT
通讯作者：
Longaker, MT
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
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作者：
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通讯作者：
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DOI：
10.1006/bbrc.2001.6270
发表时间：
2002-01-18
影响因子：
3.1
作者：
Erickson, GR;Gimble, JM;Guilak, F
通讯作者：
Guilak, F
影响因子：
2.8
作者：
CAPLAN, AI
通讯作者：
CAPLAN, AI
影响因子：
5.2
作者：
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