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Differential regulation of the bone morphogenic protein antagonist chordin in human normal and osteoarthritic chondrocytes


Objective: To investigate the distribution of the bone morphogenic protein (BMP) antagonist chordin in normal and osteoarthritic cartilage and synovial membranes, and its regulation in chondrocytes and synovial fibroblasts by inflammatory and growth factors.

Methods: Localisation of chordin in tissues was undertaken by immunohistochemistry and gene regulation was determined by real time polymerase chain reaction.

Results: In normal cartilage, chordin was found at low levels (mean (SD), 7.6 (1.3)%), mainly in the very superficial layers. In osteoarthritis, chordin was also found in the superficial layers (8.9 (1.1)%), though at a significantly higher level (24.7 (1.5)%) in the last two thirds of the cartilage. In contrast to normal cells, chordin mRNA and protein levels were significantly downregulated (p<0.01) in osteoarthritic chondrocytes by all the growth factors tested. Interferon γ stimulated chordin expression in normal but not in osteoarthritic chondrocytes (p<0.0002), while interleukin 1β and tumour necrosis factor α did not affect the expression level. However, no difference was found in either the distribution or regulation of chordin in normal and osteoarthritic synovial membranes or synovial fibroblasts.

Conclusions: The differential distribution and regulation of chordin in normal and osteoarthritic cartilage and chondrocytes suggests an involvement of this antagonist in the osteoarthritic process.

  • Act.A, activin A
  • BMP, bone morphogenic protein
  • bFGF, basic fibroblast growth factor
  • EGF, epithelial growth factor
  • IFNγ, interferon γ
  • IL1β, interleukin 1β
  • PDGF-BB, platelet derived growth factor BB
  • TGFβ1, transforming growth factor β1
  • TNFα, tumour necrosis factor α
  • chordin
  • osteoarthritis
  • chondrocyte
  • synovial fibroblast

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