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Gene expression in human chondrocytes in late OA is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy
  1. Chris J Brew (cbrew{at}
  1. University of Manchester, United Kingdom
    1. Peter D Clegg (p.d.clegg{at}
    1. University of Liverpool, United Kingdom
      1. Ray P Boot-handford (ray.boot-handford{at}
      1. University of Manchester, United Kingdom
        1. Glynne Andrews (glynne.andrew{at}
        1. Ysbyty Gwynedd, United Kingdom
          1. Tim Hardingham (timothy.e.hardingham{at}
          1. University of Manchester, United Kingdom


            Objectives: Changes in gene expression in fibrillated and intact human OA cartilage were investigated for evidence of an altered chondrocyte phenotype and hypertrophy.

            Methods: Paired osteochondral samples were taken from a high load site and a low load site from 25 OA joints and were compared with 8 similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes were analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage.

            Results: There was a major change in chondrocyte gene expression in OA cartilage. SOX9 and aggrecan gene expression were both lower in OA (p<0.001) and collagen I and II gene expression were each increased in a subset of OA samples. The major changes in gene expression were similar at the fibrillated high loaded site and the intact low loaded site. There was no evidence of a generalised change in OA to proliferative or hypertrophic phenotype as seen in growth plate, as genes associated with either stage of differentiation were unchanged, (PTHrPr), or significantly down-regulated (collagen X (p<0.002), VEGF (p<0.02), BCL-2 (p<0-0002, matrilin-1 (p<0.001). In contrast MMP-13 was significantly up-regulated in the OA cartilage samples (p<0.003).

            Conclusions: The expression of key chondrocyte genes including aggrecan and SOX9 were changed in OA cartilage and the changes were similar in both fibrillated highly loaded and intact more lowly loaded cartilage on the same joint. However, there was no significant up-regulation of type X collagen and other genes associated with chondrocyte further differentiation and hypertrophy.

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