Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development

作者：Ning, Bo; Wang, Peng; Pei, Xinghong; Kang, Yingquan; Song, Jun; Wang, Dahui; Zhang, Wanglin; Ma, Ruixue^*

来源：International Orthopaedics, 2012, 36(3): 655-664.

DOI：10.1007/s00264-011-1315-6

• WNT SIGNALING PATHWAY
• CHONDROCYTE DIFFERENTIATION
• HUMAN OSTEOARTHRITIS
• IN-VIVO
• EXPRESSION
• ADAMTS5
• DEGRADATION
• INHIBITION
• ACTIVATION

Purpose The objective of this study was to determine the role of beta-catenin in normal postnatal articular cartilage growth and degeneration. @@@ Methods We investigated beta-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 beta-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 beta-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, beta-catenin mRNA and protein were induced (p<0.05). Moreover, LiCl-activated beta-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 beta-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/beta-catenin signalling are needed to maintain postnatal articular cartilage growth and function. In the early stages of cartilage development, activation of beta-catenin signalling is necessary for articular cartilage growth, while in adult cartilage it leads to degeneration and osteoarthritic-like chondrocytes.

• 出版日期2012-3
• 单位复旦大学