Exp Mol Med.
2008 Dec;40(6):721-727. 10.3858/emm.2008.40.6.721.
Ectopic expression of cyclooxygenase-2-induced dedifferentiation in articular chondrocytes
- Affiliations
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- 1Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Korea. ksj85@kongju.ac.kr
- 2Department of Biology, College of Natural Sciences, Changwon National University, Changwon, Korea.
- 3Department of Biology, College of Natural Science, Kyungpook National University, Daegu, Korea.
- KMID: 1072952
- DOI: http://doi.org/10.3858/emm.2008.40.6.721
Abstract
- Cyclooxygenase-2 (COX-2) is known to modulate bone metabolism, including bone formation and resorption. Because cartilage serves as a template for endochondral bone formation and because cartilage development is initiated by the differentiation of mesenchymal cells into chondrocytes (Ahrens et al., 1977; Sandell and Adler, 1999; Solursh, 1989), it is of interest to know whether COX-2 expression affect chondrocyte differentiation. Therefore, we investigated the effects of COX-2 protein on differentiation in rabbit articular chondrocyte and chick limb bud mesenchymal cells. Overexpression of COX-2 protein was induced by the COX-2 cDNA transfection. Ectopic expression of COX-2 was sufficient to causes dedifferentiation in articular chondrocytes as determined by the expression of type II collagen via Alcian blue staining and Western blot. Also, COX-2 overexpression caused suppression of SOX-9 expression, a major transcription factor that regulates type II collagen expression, as indicated by the Western blot and RT-PCR. We further examined ectopic expression of COX-2 in chondrifying mesenchymal cells. As expected, COX-2 cDNA transfection blocked cartilage nodule formation as determined by Alcian blue staining. Our results collectively suggest that COX-2 overexpression causes dedifferentiation in articular chondrocytes and inhibits chondrogenic differentiation of mesenchymal cells.
Keyword
MeSH Terms
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Animals
Cartilage, Articular/cytology
Cell Differentiation
Cells, Cultured
Chick Embryo
Chondrocytes/*cytology/enzymology
Chondrogenesis
Collagen Type II/metabolism
Cyclooxygenase 2/*biosynthesis/genetics
Interleukin-1beta/pharmacology
Mesenchymal Stem Cells/*cytology/enzymology
Rabbits
SOX9 Transcription Factor/metabolism
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