Altered gene expression in articular chondrocytes of Smad3(ex8/ex8) mice, revealed by gene profiling using...

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-beta (TGF-beta)/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/ex8) and wild-type mice on day five after birth. The gene profiling results showed that the activity of bone morphogenetic protein (BMP) and TGF-beta/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 (Igf1) 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.