title: Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pediatric Orthopaedics, Children's Hospital of Fudan University, 399 Wanyuan Road, 201102, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ning
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Xinghong
authors.initials: X
authors.lastname: Pei
authors.forename: Yingquan
authors.initials: Y
authors.lastname: Kang
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.forename: Dahui
authors.initials: D
authors.lastname: Wang
authors.forename: Wanglin
authors.initials: W
authors.lastname: Zhang
authors.forename: Ruixue
authors.initials: R
authors.lastname: Ma
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002357:Cartilage Diseases / Q000235:genetics*; D002358:Cartilage, Articular / Q000166:cytology* / Q000254:growth & development; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018021:Lithium Chloride / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000276:Adjuvants, Immunologic; D024121:Collagen Type X; D051176:beta Catenin; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C518696:Adamts5 protein, rat; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; D018021:Lithium Chloride