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01.03.2012 | Original Paper | Ausgabe 3/2012

International Orthopaedics 3/2012

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

Zeitschrift:
International Orthopaedics > Ausgabe 3/2012
Autoren:
Bo Ning, Peng Wang, Xinghong Pei, Yingquan Kang, Jun Song, Dahui Wang, Wanglin Zhang, Ruixue Ma

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.

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