SMAD3介导TGF-β1刺激软骨细胞增殖和抑制软骨细胞肥大性分化(英文)

TGF-β1 Mediated by SMAD3 Stimulates Proliferation and Inhibits Hypertrophic Differentiation of Chondrocytes

为研究TGF β1 SMAD3信号对小鼠软骨细胞增殖和分化的影响 ,分离了野生型与Smad3基因剔除 (Smad3ex8 ex8)突变纯合子小鼠肋骨软骨细胞并进行了体外培养 .通过3 H TdR参入实验检测了体外培养软骨细胞的增殖能力 .TGF β1可以刺激野生型软骨细胞的增殖 ,Smad3基因缺失导致小鼠软骨细胞丧失对TGF β1刺激生长作用的应答 .Northern杂交显示 ,TGF β1促进野生型小鼠软骨细胞表达Ⅱ型胶原 ,而Smad3基因缺失突变纯合子软骨细胞大量表达肥大性软骨细胞的分子标记物X型胶原 .结果表明 ,SMAD3介导转化生长因子TGF

To investigate the roles of TGF β1 mediated by SMAD3 in proliferation and differentiation of murine chondrocytes,chondrocytes were isolated from rib cartilage of wild type and Smad3 targeted disruption ( Smad3 ex8/ex8 ) mutant mice and cultured in vitro . The proliferation capacity of the cultured chondrocytes was tested using 3 H TdR incorporation assay. Expression of type Ⅱ collagen and type X collagen of the primary cultured chondrocytes were examined by Northern blotting. The results showed that TGF β1 could stimulate wild type chondrocytes to proliferate. The deficiency of Smad3 gene resulted in impaired response of murine chondrocytes to TGF β1. TGF β1 could increase the mRNA expression of type II collagen in wild type chondrocytes, while Smad3 ex8/ex8 mutant chondrocytes strongly expressed type X collagen, a marker of hypertrophic chondrocytes. All these data suggested that SMAD3 could mediate the TGF β1 signal to stimulate the proliferation and inhibit the hypertrophic differentiation of chondrocytes.