Altered gene expression in articular chondrocytes of Smad3(ex8/ex8) mice, revealed by gene profiling using microarrays.
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.
Wang
Hao
H
Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China.
Zhang
Jishuai
J
Sun
Qiang
Q
Yang
Xiao
X
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology*; D002453:Cell Cycle; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004579:Electron Transport / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D013006:Growth Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; C519530:insulin-like growth factor-1, mouse; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D045726:Metalloproteases