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Proceedings of the Irish Soc for Rheumatology and Irish Rheumatology Health
Professionals Society AGM September 2006
Saturday, 16 th September 2006
6. ORAL PRESENTATION: Plenary Session
OMEGA-3 FATTY ACIDS REDUCE PRODUCTION OF PRO-
INFLAMMATORY PROSTANOIDS PGE 2 AND PROSTACYCLIN, AND
INCREASE PRODUCTION OF ANTI-INFLAMMATORY 15D-PGJ 2 BY
OSTEOARTHRITIC SYNOVIAL FIBROBLASTS TREATED WITH
BASIC CALCIUM PHOSPHATE CRYSTALS
B. McDonnell 1 , E.S. Molloy 1,2 , J. O’Byrne 3 , M.P. Morgan 1 , G.M. McCarthy 1,4
1 Department of Molecular and Cellular Therapeutics, Royal College of
Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland, 2 Department of
Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland,
Ohio, USA, 3 National Orthopaedic Hospital, Cappagh, Dublin 15, Ireland,
4 Department of Rheumatology, Mater Misericordiae University Hospital, Eccles
St., Dublin 7, Ireland
Aim: Intra-articular basic calcium phosphate (BCP) crystals are implicated in
osteoarthritis (OA) and amplify prostaglandin E 2 (PGE 2 ) and prostacyclin
production in osteoarthritic synovial fibroblasts (OASF). 1 Eicosapentanoic acid
(EPA) and docosahexanoic acid (DHA) are metabolised by cyclooxygenase
enzymes and appear to have anti-inflammatory effects in arthritis. 2 We
investigated the effect of omega-3 fatty acids on PG production in OASF cells
treated with BCP crystals.
Method: OASF obtained at the time of joint replacement surgery were cultured
in monolayer. Quiescent cells were enriched with EPA or DHA (50µM) for
24hours prior to stimulation with BCP crystals (18µg/cm 2 ). PG production was
measured by enzyme immuno-assay and statistically analysed using the
unpaired T-test.
Results: Treatment with BCP crystals resulted in increased PGE 2 and
prostacyclin production in OASF by approximately 10-fold and 5-fold
respectively over untreated cells, with maximal induction after 4hours.
Treatment of BCP-stimulated OASF with EPA and DHA (50µM) resulted in a
statistically significant (p≤0.05) reduction in PGE 2 and prostacyclin levels at
4hours. DHA treatment also resulted in a three-fold increase in production of
15d-PGJ 2 , in contrast to a small increase (0.5 fold) in EPA treated cells.
Conclusions: EPA and DHA reduce the pro-inflammatory effects of BCP
crystals on OASF cells via a reduction in PGE 2 . Production of prostacylin
which is implicated in inflammation, nociception and angiogenesis is also
reduced. The increased production of 15d-PGJ2 may enhance an antiinflammatory
effect through its role as an endogenous ligand for the intranuclear
receptor PPARgamma and we propose to investigate this further. These data
highlight the potential beneficial effects of omega-3 fatty acids in BCP-crystal
associated OA.