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Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy
  1. C J Brew1,
  2. P D Clegg1,2,
  3. R P Boot-Handford1,
  4. J G Andrew3,
  5. T Hardingham1
  1. 1
    Wellcome Trust Centre for Cell-Matrix Research and, Faculty of Life Sciences, University of Manchester, Manchester, UK
  2. 2
    Faculty of Veterinary Sciences, University of Liverpool Veterinary Teaching Hospital, Leahurst, Neston, UK
  3. 3
    Ysbyty Gwynedd, Penrhosgarnedd, Bangor, UK
  1. Correspondence to Professor P D Clegg, Faculty of Veterinary Sciences, University of Liverpool Veterinary Teaching Hospital, Leahurst, Neston CH64 7TE, UK; p.d.clegg{at}liv.ac.uk

Abstract

Objectives: To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage 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 eight similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes was 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 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p<0.001), and collagen I (17-fold) and II (2.5-fold) 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 the growth plate, as genes associated with either stage of differentiation were unchanged (PTHrPR), or significantly downregulated (collagen X (14-fold, p<0.002), VEGF (23-fold, p<0.02), BCL-2 (5.6-fold, p<0.001), matrilin-1 (6.5-fold, p<0.001)). In contrast MMP-13 was significantly upregulated in the OA cartilage samples (5.3-fold, p<0.003).

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

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Footnotes

  • Funding Funding from Arthritis Research Campaign (Clinical Research Training Fellowship to CJB), the Wellcome Trust (Research Leave Fellowship GR067462MA to PDC) and the Wellcome Trust for support for The Wellcome Trust Centre for Cell-Matrix Research and the Research Councils (BBSRC, MRC, EPSRC) for support for UK Centre for Tissue Engineering.

  • Competing interests None.

  • Ethics approval Approval from the Greater Manchester Ethics Committee.

  • Patient consent Patient consent received.

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