title: Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype.
abstract: Osteoarthritis (OA) is a degenerative cartilage disease with varying degrees of severity within a given joint. The purpose of this study was to define a sampling procedure for comparing human minimal and advanced OA cartilage in the same patient and to determine basic patterns of gene expression in these regions. A specific hypothesis under study was that the expression level of Bcl-2 would correlate with Sox9 and aggrecan mRNA expression in vivo as has been demonstrated in vitro. Femoral condylar advanced OA cartilage was located within 1cm of overt lesions, and minimal cartilage was taken from areas with no obvious surface defects. Histological sections were scored for disease severity and chondroitin sulfate and hydroxyproline content was determined. The expression level of nine specific genes (aggrecan, collagen type II, Bcl-2, Sox9, Link protein, osteopontin, and MMP-13, -3, and -9) was determined by quantitative real time PCR. The scores for fibrillation, chondrocyte cloning, and proteoglycan depletion were significantly different between advanced and minimal OA cartilage. The advanced OA cartilage had significantly less chondroitin sulfate than the minimal OA cartilage. Osteopontin mRNA expression showed a 3.6-fold increase in advanced compared to minimal OA cartilage. In contrast, the level of mRNA coding for aggrecan, link protein, Bcl-2, Sox9 and MMP-3, -9, -13 were all decreased in advanced compared to minimal cartilage in the majority of the patients studied. Collagen type II mRNA expression displayed a wide-range of variation. A statistically significant correlation was observed both between Bcl-2 and Sox9 mRNA level, and between Bcl-2 and aggrecan mRNA expression. The patient matched comparison of minimal and advanced OA cartilage revealed differences in cellular and tissue characteristics, and changes in gene expression that may be involved in OA progression. In addition, Bcl-2 may also play a role in regulating the expression of aggrecan through Sox9 in vivo as well as in vitro.
authors.affiliation: Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA.
authors.forename: Rieko
authors.initials: R
authors.lastname: Yagi
authors.forename: Denise
authors.initials: D
authors.lastname: McBurney
authors.forename: David
authors.initials: D
authors.lastname: Laverty
authors.forename: Scott
authors.initials: S
authors.lastname: Weiner
authors.forename: Walter E
authors.initials: WE
authors.lastname: Horton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics; D020869:Gene Expression Profiling; D006025:Glycosaminoglycans / Q000032:analysis; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D010003:Osteoarthritis / Q000378:metabolism*; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000235:genetics
chemical_list: D024043:Collagen Type II; D006025:Glycosaminoglycans; D006609:High Mobility Group Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9