Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway.
Our previous study indicated that interleukin (IL)-1beta induces expression of several Wnt proteins in chondrocytes and causes chondrocyte dedifferentiation via the c-Jun/activator protein-1 (AP-1) pathway. This study examined whether Wnt-3a causes chondrocyte dedifferentiation via the c-Jun/AP-1 pathway. Wnt-3a inhibited chondrogenesis of mesenchymal cells by stabilizing cell-cell adhesion in a manner independent of beta-catenin transcriptional activity. Wnt-3a also induced dedifferentiation of articular chondrocytes by stimulating the transcriptional activity of beta-catenin-T cell-factor/lymphoid-enhancer-factor (Tcf/Lef) complex. In chondrocytes, Wnt-3a caused the expression of c-Jun and its phosphorylation by c-Jun N-terminal kinase (JNK), resulting in activation of AP-1. AP-1 activation suppressed the expression of Sox-9, a major transcription factor regulating type II collagen expression. Collectively, our results suggest that Wnt-3a inhibits chondrogenesis by stabilizing cell-cell adhesion and that it causes dedifferentiation of chondrocytes by activating of beta-catenin-Tcf/Lef transcriptional complex and the c-Jun/AP-1 pathway.
Hwang
Sang-Gu
SG
Department of Life Science, Gwangju Institute of Science and Technology, Buk-Gu, Gwangju 500-712, Korea.
Yu
Sung-Sook
SS
Lee
Soo-Woong
SW
Chun
Jang-Soo
JS
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology*; D024043:Collagen Type II / Q000378:metabolism; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D024043:Collagen Type II; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011506:Proteins; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D048031:JNK Mitogen-Activated Protein Kinases