Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
Tóm tắt
In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation. Two specific n-3 compounds were tested, namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), each at 0.1, 1 and 10 μM. Full thickness bovine cartilage explants, 5 mm in diameter, were cultured for 5 days with or without IL-1β and in the presence or absence of each n-3 compound. The media were replaced every 24 hours and assayed for sGAG content using the 1,9-dimethylmethylene blue (DMB) method. Chondrocyte viability was determined at the end of the culture period using fluorescence microscopy to visualise cells labelled with calcein AM and ethidium homodimer. Treatment with IL-1β (10 ng.ml-1) produced a large increase in sGAG release compared to untreated controls, but with no effect on cell viability, which was maintained above 80% for all treatments. In the absence of IL-1β, both n-3 compounds induced a mild catabolic response with increased loss of sGAG, particularly at 10 μM. By contrast, in the presence of IL-1β, both EPA and DHA at 0.1 and 1 μM significantly reduced IL-1β-mediated sGAG loss. The efficacy of the EPA treatment was maintained at approximately 75% throughout the 5-day period. However, at the same concentrations, the efficacy of DHA, although initially greater, reduced to approximately half that of EPA after 5 days. For both EPA and DHA, the highest dose of 10 μM was less effective. The results support the hypothesis that n-3 compounds are anti-inflammatory through competitive inhibition of the arachidonic acid oxidation pathway. The efficacy of these compounds is likely to be even greater at more physiological levels of IL-1β. Thus we suggest that n-3 PUFAs, particularly EPA, have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory joint disease.
Tài liệu tham khảo
Huang K, Wu LD: Aggrecanase and aggrecan degradation in osteoarthritis: a review. J Int Med Res. 2008, 36: 1149-1160.
Caterson B, Flannery CR, Hughes CE, Little CB: Mechanisms involved in cartilage proteoglycan catabolism. Matrix Biol. 2000, 19: 333-344. 10.1016/S0945-053X(00)00078-0.
Lohmander LS, Ionescu M, Jugessur H, Poole AR: Changes in joint cartilage aggrecan after knee injury and in osteoarthritis. Arthritis Rheum. 1999, 42: 534-544. 10.1002/1529-0131(199904)42:3<534::AID-ANR19>3.0.CO;2-J.
Struglics A, Larsson S, Pratta MA, Kumar S, Lark MW, Lohmander LS: Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments. Osteoarthritis Cartilage. 2006, 14: 101-113. 10.1016/j.joca.2005.07.018.
Pearle AD, Scanzello CR, George S, Mandl LA, DiCarlo EF, Peterson M, Sculco TP, Crow MK: Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage. 2007, 15: 516-523. 10.1016/j.joca.2006.10.010.
Goldring MB, Otero M, Tsuchimochi K, Ijiri K, Li Y: Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann Rheum Dis. 2008, 67 (Suppl 3): iii75-iii82. 10.1136/ard.2008.098764.
Caterson B, Flannery CR, Hughes CE, Little CB: Mechanisms of proteoglycan metabolism that lead to cartilage destruction in the pathogenesis of arthritis. Drugs Today (Barc). 1999, 35: 397-402.
Amin AR: Regulation of tumor necrosis factor-α and tumor necrosis factor converting enzyme in human osteoarthritis. Osteoarthritis Cartilage. 1999, 7: 392-394. 10.1053/joca.1998.0221.
Lotz M: Cytokines in cartilage injury and repair. Clin Orthop Relat Res. 2001, 391 (Suppl): S108-S115. 10.1097/00003086-200110001-00011.
Vincenti MP, Brinckerhoff CE: Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1β. Arthritis Res. 2001, 3: 381-388. 10.1186/ar331.
Little CB, Flannery CR, Hughes CE, Goodship A, Caterson B: Cytokine induced metalloproteinase expression and activity does not correlate with focal susceptibility of articular cartilage to degeneration. Osteoarthritis Cartilage. 2005, 13: 162-170. 10.1016/j.joca.2004.10.014.
Little CB, Mittaz L, Belluoccio D, Rogerson FM, Campbell IK, Meeker CT, Bateman JF, Pritchard MA, Fosang AJ: ADAMTS-1-knockout mice do not exhibit abnormalities in aggrecan turnover in vitro or in vivo. Arthritis Rheum. 2005, 52: 1461-1472. 10.1002/art.21022.
Zainal Z, Longman AJ, Hurst S, Duggan K, Caterson B, Hughes CE, Harwood JL: Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis. Osteoarthritis Cartilage. 2009, 17: 896-905. 10.1016/j.joca.2008.12.009.
Watanabe Y, Namba A, Honda K, Aida Y, Matsumura H, Shimizu O, Suzuki N, Tanabe N, Maeno M: IL-1β stimulates the expression of prostaglandin receptor EP4 in human chondrocytes by increasing production of prostaglandin E2. Connect Tissue Res. 2009, 50: 186-193. 10.1080/03008200802588451.
Burr G, Burr M: On the nature and role of fatty acids essential in nutrition. J Biol Chem. 1930, 86: 587-621.
Das UN: Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?. Prostaglandins Leukot Essent Fatty Acids. 2000, 63: 351-362. 10.1054/plef.2000.0226.
Simopoulos AP: Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991, 54: 438-463.
Michael-Titus AT: Omega-3 fatty acids and neurological injury. Prostaglandins Leukot Essent Fatty Acids. 2007, 77: 295-300. 10.1016/j.plefa.2007.10.021.
Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J: n-3 Fatty acids from fish or fish-oil supplements, but not α-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006, 84: 5-17.
Cleland LG, James MJ: Fish oil and rheumatoid arthritis: antiinflammatory and collateral health benefits. J Rheumatol. 2000, 27: 2305-2307.
Roush JK, Dodd CE, Fritsch DA, Allen TA, Jewell DE, Schoenherr WD, Richardson DC, Leventhal PS, Hahn KA: Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc. 2010, 236: 59-66. 10.2460/javma.236.1.59.
Hankenson KD, Watkins BA, Schoenlein IA, Allen KG, Turek JJ: Omega-3 fatty acids enhance ligament fibroblast collagen formation in association with changes in interleukin-6 production. Proc Soc Exp Biol Med. 2000, 223: 88-95. 10.1046/j.1525-1373.2000.22312.x.
Flower RJ, Perretti M: Controlling inflammation: a fat chance?. J Exp Med. 2005, 201: 671-674. 10.1084/jem.20050222.
Bloomer RJ, Larson DE, Fisher-Wellman KH, Galpin AJ, Schilling BK: Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study. Lipids Health Dis. 2009, 8: 36-10.1186/1476-511X-8-36.
Farndale RW, Sayers CA, Barrett AJ: A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Connect Tissue Res. 1982, 9: 247-248. 10.3109/03008208209160269.
Clutterbuck AL, Mobasheri A, Shakibaei M, Allaway D, Harris P: Interleukin-1β-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation. Ann NY Acad Sci. 2009, 1171: 428-435. 10.1111/j.1749-6632.2009.04687.x.
Kojima F, Naraba H, Miyamoto S, Beppu M, Aoki H, Kawai S: Membrane-associated prostaglandin E synthase-1 is upregulated by proinflammatory cytokines in chondrocytes from patients with osteoarthritis. Arthritis Res Ther. 2004, 6: R355-365. 10.1186/ar1195.
Chowdhury TT, Arghandawi S, Brand J, Akanji OO, Bader DL, Salter DM, Lee DA: Dynamic compression counteracts IL-1β induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs. Arthritis Res Ther. 2008, 10: R35-10.1186/ar2389.
Arner EC, Hughes CE, Decicco CP, Caterson B, Tortorella MD: Cytokine-induced cartilage proteoglycan degradation is mediated by aggrecanase. Osteoarthritis Cartilage. 1998, 6: 214-228. 10.1053/joca.1998.0114.
Zhao TZ, Xia YZ, Li L, Li J, Zhu G, Chen S, Feng H, Lin JK: Bovine serum albumin promotes IL-1β and TNF-α secretion by N9 microglial cells. Neurol Sci. 2009, 30: 379-383. 10.1007/s10072-009-0123-x.
Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH: Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr. 2000, 130: 1925-1931.
Sethi S: Inhibition of leukocyte-endothelial interactions by oxidized omega-3 fatty acids: a novel mechanism for the anti-inflammatory effects of omega-3 fatty acids in fish oil. Redox Rep. 2002, 7: 369-378. 10.1179/135100002125001144.
Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN: Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med. 2005, 201: 713-722. 10.1084/jem.20042031.
Schwab JM, Chiang N, Arita M, Serhan CN: Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature. 2007, 447: 869-874. 10.1038/nature05877.
Blain EJ, Ali AY, Duance VC: Boswellia frereana (frankincense) suppresses cytokine-induced matrix metalloproteinase expression and production of pro-inflammatory molecules in articular cartilage. Phytother Res. 2010, 24: 905-912.