Regulation of type II collagen expression by cyclin-dependent kinase 6, cyclin D1, and p21 in articular chondrocytes.
This study examined whether cell cycle regulatory proteins, such as cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors, regulate type II collagen expression and mediate interlukin-1 (IL-1beta)-induced suppression of type II collagen expression in articular chondrocytes. IL-1beta inhibited type II collagen expression, but activated CDK6. Ectopic expression of CDK2 did not alter type II collagen expression. However, overexpression of CDK6 inhibited type II collagen expression, whereas inhibition of CDK6 activity blocked IL-1beta-induced suppression of type II collagen expression. IL-1beta upregulated the expression of cyclin D1, which is known to activate CDK6. In turn, overexpression of cyclin D1 suppressed type II collagen expression. In contrast to cyclin D1, IL-1beta triggered down-regulation of the CDK inhibitor, p21. Overexpression of p21 blocked IL-1beta- or CDK6-induced suppression of type II collagen expression. Our results collectively indicate that CDK6/cyclin D1/p21 complex regulates type II collagen expression in articular chondrocytes.
Hwang
Sang-Gu
SG
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea.
Song
Sung-Min
SM
Kim
Jeong-Ran
JR
Park
Chun-Shik
CS
Song
Woo-Keun
WK
Chun
Jang-Soo
JS
D000818:Animals; D015153:Blotting, Western; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000096:biosynthesis*; D019938:Cyclin D1 / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2 / Q000502:physiology; D051361:Cyclin-Dependent Kinase 6 / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology*; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D011817:Rabbits
D024043:Collagen Type II; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053583:Interleukin-1beta; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D051361:Cyclin-Dependent Kinase 6; D048031:JNK Mitogen-Activated Protein Kinases