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Anti-tumor necrosis factor therapy increases synovial osteoprotegerin expression in rheumatoid arthritis

Anca Irinel Catrina1, Erik af Klint, Sofia Ernestam

  • 1Rheumatology Research Laboratory, Karolinska University Hospital, Karolinska Institutet, S-17176 Stockholm, Sweden. Anca.Catrina@ki.se

Arthritis and Rheumatism
|December 31, 2005
PubMed
Abstract

Insights

Tumor necrosis factor (TNF) blockers increase osteoprotegerin (OPG) and decrease the receptor activator of NF-kappaB ligand (RANKL) to OPG ratio in rheumatoid arthritis (RA) patients. This modulation of the OPG/RANKL system may explain reduced radiographic progression.

Area of Science:

  • Rheumatology and immunology research.
  • Cell biology and molecular mechanisms of inflammation.

Background:

  • Tumor necrosis factor (TNF)-blocking agents like etanercept and infliximab reduce radiographic progression in rheumatoid arthritis (RA).
  • The precise mechanism behind TNF inhibitors' protective effect against RA joint damage remains unclear.
  • Understanding the role of osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in RA pathogenesis is crucial.

Purpose of the Study:

  • To investigate the impact of anti-TNF therapy on OPG and RANKL expression in RA synovial tissue.
  • To elucidate the molecular mechanisms underlying the radiographic protection offered by TNF antagonists.

Main Methods:

  • Immunohistochemistry was used to assess OPG and RANKL expression in synovial biopsy specimens from 18 RA patients before and after treatment.
  • Patients received either etanercept or infliximab for 8 weeks.
  • In vitro studies utilized Western blotting to evaluate the effect of TNF antagonists on OPG and RANKL in osteoblasts and endothelial cells.

Main Results:

  • Both etanercept and infliximab treatments significantly increased OPG expression in RA synovial tissue.
  • RANKL expression remained unchanged in both treatment groups after 8 weeks.
  • The RANKL:OPG ratio decreased in patients treated with TNF antagonists, an effect mirrored in vitro.

Conclusions:

  • Anti-TNF therapy in RA modulates the OPG/RANKL system.
  • This modulation of the OPG/RANKL balance represents a potential mechanism contributing to the observed retardation of radiographic damage in RA patients treated with TNF antagonists.

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