中文摘要：

此前发现Smad3基因敲除小鼠（Smad3^ex8/ex8）的关节软骨细胞异常肥大分化，出现类似于人类骨关节炎的表型。为了进一步明确转化生长因子-β（TGF-β）／Smad3信号通过调节哪些靶基因的表达来抑制关节软骨细胞的肥大分化，以及研究骨关节炎发病的分子机制，利用寡核苷酸芯片技术分析了5臼龄Smad3基因敲除小鼠与野生型对照小鼠关节软骨细胞基因表达谱的改变。通过对差异表达基因的分析，发现在Smad3基因敲除小鼠软骨细胞中骨形态发生蛋白（BMP）与TGF-β／细胞分裂周期基因42（Cdc42）信号通路活性增强。此外，还发现其他信号通路，如生长激素（growth hormone）／胰岛素样生长因子1（Igfl）以及成纤维细胞生长因子（Fgf）信号通路相关基因表达的改变。值得注意的是，还发现了Smad3基因敲除小鼠软骨细胞中蛋白合成与电子传递链相关基因的表达水平普遍上调，这意味着蛋白质合成速率的加快与细胞有氧呼吸的增强可能与关节软骨细胞的肥大分化和骨关节炎的发生相关。

英文摘要：

It has been previously reported that small mother against decapentaplegic 3 （Smad3） gene knockout （Smad3^ex8/ex8） mice displays phenotypes similar to human osteoarthritis, as characterized by abnormal hypertrophic differentiation of articular chondrocytes. To further clarify the crucial target genes that mediate transformation growth factor-β （TGF-β）/Smad3 signals on articular chondrocytes differentiation and investigate the underlying molecular mechanism of osteoarthritis, microarrays were used to perform comparative transcriptional profiling in the articular cartilage between Smad3^ex8/ex8and wild-type mice on day five after birth. The gene profding results showed that the activity of bone morphogenetic protein （BMP） and TGF-β/cell division cycle 42 （Cdc42） signaling pathways were enhanced in Smad3^ex8/ex8 chondrocytes. Moreover, there was altered gene expression in growth hormone/insulin-like growth factor 1 （Igfl） axis and fibroblast growth factor （Fgf） signaling pathway. Notably, protein synthesis related genes and electron transport chain related genes were upregulated in Smad3^ex8/ex8 chondrocytes, implying that accelerated protein synthesis and enhanced cellular respiration might contribute to hypertrophic differentiation of articular chondrocytes and the pathogenesis of osteoarthritis.