Expression of proteinase-activated receptors (PAR)-2 in articular chondrocytes is modulated by IL-1beta, TNF-alpha and TGF-beta

Osteoarthritis Cartilage. 2006 Nov;14(11):1163-73. doi: 10.1016/j.joca.2006.04.015. Epub 2006 Jun 6.


Objective: To investigate the modulation of expression of proteinase-activated receptor-2 (PAR-2) in articular chondrocytes by inflammatory cytokines.

Design: Articular synovium and cartilage tissues were collected from eight patients with osteoarthritis (OA), and three patients without arthropathy ("normal"). Chondrocytes were stimulated with interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha or transforming growth factor (TGF)-beta1. The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (PCR), Western blotting and immunofluorescence. Quantitative PCR was performed to assess the expression levels of PAR-2 messenger RNA (mRNA).

Results: The expression of PAR-2 mRNA was demonstrated in both OA and normal chondrocytes as well as in synovial fibroblasts. However, the level of PAR-2 in OA chondrocytes was much higher than in normal chondrocytes. Long-term culture revealed that PAR-2 mRNA expression was maintained up to three passages in OA but not in normal chondrocytes. IL-1beta and TNF-alpha both upregulated PAR-2 expression in normal and OA chondrocytes. In contrast, TGF-beta1 significantly decreased expression of PAR-2 in OA chondrocytes but increased PAR-2 in normal chondrocytes.

Conclusions: Overexpression of PAR-2 in OA chondrocytes is upregulated by proinflammatory cytokines IL-1beta and TNF-alpha, and down-regulated by regulatory cytokine TGF-beta1. PAR-2 may be involved in the pathogenesis of OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cartilage, Articular / immunology*
  • Cell Line
  • Cell Membrane / immunology
  • Cells, Cultured
  • Chondrocytes / immunology*
  • Cytokines / immunology*
  • Cytoplasm / immunology
  • Dose-Response Relationship, Immunologic
  • Female
  • Fibroblasts / immunology
  • Humans
  • Interleukin-1beta / immunology
  • Male
  • Middle Aged
  • Osteoarthritis / immunology*
  • RNA, Messenger / analysis
  • Receptor, PAR-2 / analysis*
  • Synovial Membrane / immunology
  • Time Factors
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation / immunology


  • Cytokines
  • Interleukin-1beta
  • RNA, Messenger
  • Receptor, PAR-2
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha