Altered Gene Expression in Articular Chondrocytes of Smad3ex8/ex8 Mice, Revealed by Gene Profiling Using Microarrays

Abstract

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/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-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 (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.