Institut de Biologie et Chimie des Protéines, CNRS UMR 5086, Université de Lyon, and IFR 128 BioSciences Gerland-Lyon Sud, 7 passage du Vercors, Lyon F-69367, France.
Eur J Cell Biol. 2010 Apr;89(4):307-14. doi: 10.1016/j.ejcb.2009.10.018. Epub 2010 Feb 2.
Bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta1 are multifunctional cytokines both proposed as stimulants for cartilage repair. Thus it is crucial to closely examine and compare their effects on the expression of key markers of the chondrocyte phenotype, at the gene and protein level. In this study, the expression of alpha 10 and alpha 11 integrin subunits and the IIA/IIB spliced forms of type II procollagen have been monitored for the first time in parallel in the same in vitro model of mouse chondrocyte dedifferentiation/redifferentiation. We demonstrated that TGF-beta1 stimulates the expression of the non-chondrogenic form of type II procollagen, IIA isoform, and of a marker of mesenchymal tissues, i.e. the alpha 11 integrin subunit. On the contrary, BMP-2 stimulates the cartilage-specific form of type II procollagen, IIB isoform, and a specific marker of chondrocytes, i.e. the alpha 10 integrin subunit. Collectively, our results demonstrate that BMP-2 has a better capability than TGF-beta1 to stimulate chondrocyte redifferentiation and reveal that the relative expressions of type IIB to type IIA procollagens and alpha 10 to alpha 11 integrin subunits are good markers to define the differentiation state of chondrocytes. In addition, adenoviral expression of Smad6, an inhibitor of BMP canonical Smad signaling, did not affect expression of total type II procollagen or the ratio of type IIA and type IIB isoforms in mouse chondrocytes exposed to BMP-2. This result strongly suggests that signaling pathways other than Smad proteins are involved in the effect of BMP-2 on type II procollagen expression.
骨形态发生蛋白（BMP）-2 和转化生长因子（TGF）-β1 是多功能细胞因子，两者均被提议作为软骨修复的刺激物。因此，在基因和蛋白质水平上密切检查和比较它们对软骨细胞表型关键标志物表达的影响至关重要。在这项研究中，首次在相同的体外鼠软骨细胞去分化/再分化模型中同时监测了 alpha 10 和 alpha 11 整合素亚基以及 II 型前胶原的 IIA/IIB 剪接形式的表达。我们证明 TGF-β1 刺激非软骨形成型 II 型前胶原，IIA 同工型的表达，以及间质组织的标志物，即 alpha 11 整合素亚基。相反，BMP-2 刺激软骨特异性 II 型前胶原，IIB 同工型和软骨细胞的特异性标志物，即 alpha 10 整合素亚基的表达。总的来说，我们的结果表明 BMP-2 比 TGF-β1 更好地刺激软骨细胞再分化，并表明 IIB 型到 IIA 型前胶原和 alpha 10 到 alpha 11 整合素亚基的相对表达是定义软骨细胞分化状态的良好标志物。此外，腺病毒表达 Smad6，一种 BMP 经典 Smad 信号的抑制剂，不会影响暴露于 BMP-2 的鼠软骨细胞中总 II 型前胶原或 IIA 和 IIB 同工型的比例。这一结果强烈表明，除 Smad 蛋白以外的信号通路参与了 BMP-2 对 II 型前胶原表达的影响。
