Selective COX-2 inhibition prevents proinflammatory cytokine-induced cartilage damage

Rheumatology (Oxford). 2002 Jul;41(7):801-8. doi: 10.1093/rheumatology/41.7.801.

Abstract

Objectives: This study evaluated the in vitro effect of the selective cyclooxygenase-2 (COX) inhibitor celecoxib on cartilage matrix turnover under normal and inflammatory conditions.

Methods: Healthy human articular cartilage tissue alone, in co-culture with peripheral blood mononuclear cells (PBMC) or in the presence of interleukin 1 (IL-1beta) plus tumour necrosis factor alpha (TNF-alpha) was cultured for 7 days in the presence of celecoxib. Changes in cartilage matrix turnover were measured.

Results: No direct effects of celecoxib on healthy normal cartilage were found. Both PBMC and IL-1beta plus TNF-alpha induced strong inhibition of cartilage proteoglycan synthesis and significant enhancement of the release of proteoglycans, diminishing proteoglycan content. Celecoxib was able to reverse these adverse effects up to complete normalization.

Conclusions: The results suggest that, under the influence of inflammation, COX-2 is up-regulated, which results in disturbance of cartilage matrix turnover. Celecoxib, by diminishing COX-2 activity, prevents these adverse effects without having a direct effect on healthy cartilage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cartilage Oligomeric Matrix Protein
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Celecoxib
  • Cells, Cultured
  • Coculture Techniques
  • Cyclooxygenase Inhibitors / pharmacology*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Interleukin-1 / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Matrilin Proteins
  • Proteoglycans / biosynthesis
  • Pyrazoles
  • Sulfonamides / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation

Substances

  • Cartilage Oligomeric Matrix Protein
  • Cyclooxygenase Inhibitors
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Interleukin-1
  • Matrilin Proteins
  • Proteoglycans
  • Pyrazoles
  • Sulfonamides
  • TSP5 protein, human
  • Tumor Necrosis Factor-alpha
  • Celecoxib