Chondrogenic differentiation of bovine synovium: bone morphogenetic proteins 2 and 7 and transforming growth factor beta1 induce the formation of different types of cartilaginous tissue.
Chondrogenic differentiation of bovine synovium: bone morphogenetic proteins 2 and 7 and transforming growth factor beta1 induce the formation of different types of cartilaginous tissue.
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DOI：
10.1002/art.22701
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发表时间：
2007-06
影响因子：
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通讯作者：
N. Shintani;E. Hunziker
中科院分区：
文献类型：
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作者：
N. Shintani;E. Hunziker
目的比较骨形态发生蛋白2和骨形态发生蛋白7(BMP-2和BMP-7)和转化生长因子β1(TGFbeta1)对滑膜组织的组织学、生化和基因表达的影响。方法取小牛掌骨关节滑膜，在琼脂糖凝胶中培养。首先，BMP-2用于评估不同培养条件下滑膜外植体的软骨形成能力。在合适的条件下，比较BMP-2、BMP-7和TGFbeta1的软骨形成作用。对分化的组织进行组织学、组织形态计量学、免疫组织化学、生化和基因表达水平的表征。结果在无血清和无地塞米松的条件下，BMP-2以剂量和时间依赖的方式诱导滑膜组织向软骨细胞分化。软骨相关基因的表达水平呈时间依赖性增加。BMP-7在诱导软骨形成方面比BMP-2更强，但每种情况下分化组织的性质都是相似的。在TGFbeta1作用下形成的软骨组织的类型在细胞表型和基因表达谱上都不同。结论TGFβ超家族的3个受试成员具有不同的软骨形成潜能，可诱导形成不同类型的软骨组织。为了使滑膜外植体完全分化为典型的透明类型的关节软骨，需要进一步改进刺激条件。这可以通过同时应用几种生长因子来实现。
OBJECTIVE To compare the potential of bone morphogenetic proteins 2 and 7 (BMP-2 and BMP-7) and transforming growth factor beta1 (TGFbeta1) to effect the chondrogenic differentiation of synovial explants by analyzing the histologic, biochemical, and gene expression characteristics of the cartilaginous tissues formed. METHODS Synovial explants derived from the metacarpal joints of calves were cultured in agarose. Initially, BMP-2 was used to evaluate the chondrogenic potential of the synovial explants under different culturing conditions. Under appropriate conditions, the chondrogenic effects of BMP-2, BMP-7, and TGFbeta1 were then compared. The differentiated tissue was characterized histologically, histomorphometrically, immunohistochemically, biochemically, and at the gene expression level. RESULTS BMP-2 induced the chondrogenic differentiation of synovial explants in a dose- and time-dependent manner under serum- and dexamethasone-free conditions. The expression levels of cartilage-related genes increased in a time-dependent manner. BMP-7 was more potent than BMP-2 in inducing chondrogenesis, but the properties of the differentiated tissue were similar in each case. The type of cartilaginous tissue formed under the influence of TGFbeta1 differed in terms of both cell phenotype and gene expression profiles. CONCLUSION The 3 tested members of the TGFbeta superfamily have different chondrogenic potentials and induce the formation of different types of cartilaginous tissue. To effect the full differentiation of synovial explants into a typically hyaline type of articular cartilage, further refinement of the stimulation conditions is required. This might be achieved by the simultaneous application of several growth factors.