Ectopic expression of cyclooxygenase-2-induced dedifferentiation in articular chondrocytes.
10.3858/emm.2008.40.6.721
- Author:
Won Kil LEE
1
;
Seon Mi YU
;
Seon Woo CHEONG
;
Jong Kyung SONN
;
Song Ja KIM
Author Information
1. Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Korea. ksj85@kongju.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
chondrocytes;
cyclooxygenase 2;
cell dedifferentiation;
cell differentiation;
collagen type II;
mesenchymal cells
- MeSH:
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
- From:Experimental & Molecular Medicine
2008;40(6):721-727
- CountryRepublic of Korea
- Language:English
-
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.
