title: Expression of Sox9 and type IIA procollagen during attempted repair of articular cartilage damage in a transgenic mouse model of osteoarthritis.
abstract: OBJECTIVE
  To determine the capacity of chondrocytes in aging and degenerating articular cartilage to produce major components of the extracellular matrix and maintain the normal structure of articular cartilage in a transgenic mouse model of osteoarthritis.
  
  
  METHODS
  Transcription factor Sox9 was used as an indicator of the activation and maintenance of the articular chondrocyte phenotype. Knee joints of Del1 mice carrying 6 copies of the pro alpha1(II) collagen transgene with a short deletion mutation were analyzed at the age of 10 days and at 2, 3, 4, 6, 9, and 15 months by Northern hybridization, RNase protection assay, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. Nontransgenic littermates were used as controls.
  
  
  RESULTS
  We demonstrated the presence of Sox9 in articular chondrocytes during development, growth, and aging, with the highest messenger RNA levels during the period of rapid growth. With the appearance of degenerative lesions in articular cartilage, 2 repair processes were observed. Local proliferation and activation of chondrocytes rich in Sox9, surrounded by type IIA procollagen and proteoglycans, was seen in articular cartilage. In contrast, metabolically inactive chondrocytes were observed at the margins of the defects. They were devoid of Sox9 and were surrounded by a proteoglycan-poor matrix. Sometimes, the lesions were filled with repair tissue that contained type III collagen but little proteoglycan or type II collagen.
  
  
  CONCLUSIONS
  The results indicate that chondrocytes in mature articular cartilage are capable of inducing the production of Sox9 and type IIA procollagen, which is typical of early chondrogenesis. Degenerative defects in the knee joints of transgenic Del1 mice are associated with local activation of chondrocytes, which probably contributes to the repair process. In other areas, the repair process produces a noncartilaginous matrix, which is insufficient to maintain the integrity of articular cartilage and which allows degeneration to proceed.
authors.affiliation: University of Turku, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Salminen
authors.forename: E
authors.initials: E
authors.lastname: Vuorio
authors.forename: A M
authors.initials: AM
authors.lastname: Säämänen
mesh_terms: D053674:Aggrecans; D000375:Aging / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins; D019084:Fluorescent Antibody Technique, Indirect; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C508320:Acan protein, mouse; D053674:Aggrecans; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D006609:High Mobility Group Proteins; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011347:Procollagen; D011509:Proteoglycans; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; C109195:procollagen type IIA amino-terminal peptide; D003094:Collagen