Ectopic expression of cyclooxygenase-2-induced dedifferentiation in articular chondrocytes.
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.
Lee
Won Kil
WK
Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju 314-701, Korea.
Yu
Seon Mi
SM
Cheong
Seon Woo
SW
Sonn
Jong Kyung
JK
Kim
Song Ja
SJ
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology* / Q000201:enzymology; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D053583:Interleukin-1beta / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D011817:Rabbits; D055758:SOX9 Transcription Factor / Q000378:metabolism
D024043:Collagen Type II; D053583:Interleukin-1beta; D055758:SOX9 Transcription Factor; D051546:Cyclooxygenase 2