1. Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development.
- Author
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Ning B, Wang P, Pei X, Kang Y, Song J, Wang D, Zhang W, and Ma R
- Subjects
- ADAM Proteins genetics, ADAM Proteins metabolism, ADAMTS4 Protein, ADAMTS5 Protein, Adjuvants, Immunologic pharmacology, Animals, Apoptosis drug effects, Cartilage, Articular growth & development, Cells, Cultured, Chondrocytes drug effects, Chondrocytes metabolism, Collagen Type X genetics, Collagen Type X metabolism, Gene Expression drug effects, Lithium Chloride pharmacology, Matrix Metalloproteinase 13, Procollagen N-Endopeptidase genetics, Procollagen N-Endopeptidase metabolism, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, beta Catenin biosynthesis, Cartilage Diseases genetics, Cartilage, Articular cytology, Chondrocytes cytology, Gene Expression physiology, Gene Expression Regulation, Developmental drug effects, beta Catenin genetics
- Abstract
Purpose: The objective of this study was to determine the role of β-catenin in normal postnatal articular cartilage growth and degeneration., Methods: We investigated β-catenin gene and protein expression in hip cartilage cells of normal Wistar rats at two, four, six and eight weeks of age by using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary articular chondrocytes from eight week old rats were cultured and treated with LiCl for activation of β-catenin. Collagen X and matrix metalloproteinase 13 (MMP-13) were detected by quantitative RT-PCR and immunofluorescence. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and 5 were detected by quantitative RT-PCR, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used for detecting cell apoptosis., Results: The highest levels of β-catenin expressions were detected in two week old rats, after which a steady decline was observed over the remaining period of observation (p < 0.05). When primary articular chondrocytes from eight week old rats were treated with LiCl, β-catenin mRNA and protein were induced (p < 0.05). Moreover, LiCl-activated β-catenin in chondrocytes was associated with significant concomitant increases in mRNA expression of collagen X and the MMP-13 encoding collagenase 3. Significantly increased mRNA expression of ADAMTS-5 was also seen in primary chondrocytes from eight week old rats after LiCl treatment (p < 0.05). The effect was specific to ADAMTS-5 since ADAMTS-4, which has similar proteolytic activity but different aggrecanase activity, was unaffected. Finally, TUNEL staining revealed that LiCl-activated β-catenin signalling led to increased cell apoptotic events in chondrocytes (p < 0.05)., Conclusions: Our findings suggest that normal spatiotemporal patterns and degrees of Wnt/β-catenin signalling are needed to maintain postnatal articular cartilage growth and function. In the early stages of cartilage development, activation of β-catenin signalling is necessary for articular cartilage growth, while in adult cartilage it leads to degeneration and osteoarthritic-like chondrocytes.
- Published
- 2012
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