Anti-inflammatory effects of an injectable copolymer of fatty acids (Ara 3000 beta®) in joint diseases

Journal of Inflammation

Karim Boumediene¹  Gérard Ewert²  Céline Quesnelle¹  Nicolas Girard¹  Eva Lhuissier¹  Catherine Baugé¹ 

[1] UNICAEN, EA4652 MILPAT UFR de médecine, Université de Caen, Caen cedex 5, Caen, CS14032, France;Sexmoor Laboratoires, 13 120 Saint Remy de Provence, France

关键词: Joints;    MMPs;    Osteoarthritis;    Arthritis;    Inflammation;    Gene expression;    Fatty acid;    Extracellular matrix;    Drug therapy;    Cytokines;   

Others  :  1134143
DOI  :  10.1186/s12950-015-0062-7

 received in 2014-08-14, accepted in 2015-02-16,  发布年份 2015

【 摘 要 】

Background

In inflammatory joint disease, such as osteoarthritis or arthritis, there is an increased level of pro-inflammatory cytokines, such as interleukin-1β. These cytokines stimulate the expression and release of matrix metalloproteases (MMP), leading to the degradation of cartilage extracellular matrix and subsequently mobility difficulty and suffering for patients. The aim of this study was to examine the therapeutic potential of a fatty acid copolymer in in vitro and in vivo models of cartilage inflammation.

Methods

Inflammation was mimicked in vitro by treatment of human articular chondrocytes with interleukin-1β. Effects of a co-treatment with a copolymer of fatty acids (Ara 3000 beta®) were determined by evaluating MMP production by RT-PCR and ELISA, NO release by Griess assay, and PGE2 expression by ELISA. In addition, in vivo analysis (evolution of weight and edema) were also performed after injection of Freund adjuvant in rats treated or not with the copolymer of fatty acids.

Results

The copolymer of fatty acids clearly reduces inflammation in joint. In vitro, it impairs IL1 stimulated-MMP production and release, as well as the release of NO and PGE2 and the activation of NFκB. Furthermore, in vivo experiments using adjuvant induced-arthritis corroborates the anti-inflammatory effects of the copolymer of fatty acids, with a reduction of edemas, erythemas and ankylosis in arthritic rats.

Conclusions

The results support the hypothesis that a copolymer of fatty acids, such as Ara 3000 beta®, is a powerful anti-inflammatory compounds, suggesting that it has a potential for preventing cartilage degradation associated with chronic inflammatory joint disease.

【 授权许可】

   
2015 Baugé et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Pearle AD, Scanzello CR, George S, Mandl LA, DiCarlo EF, Peterson M, et al.: Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthr Cartil OARS Osteoarthr Res Soc 2007, 15:516-23.
• [2]Baugé C, Boumédiene K: Interleukin-1 in osteoarthritis. In Adv Genet Res 2013, 10:115-28. Nova publication
• [3]Stitik TP, Altschuler E, Foye PM: Pharmacotherapy of osteoarthritis. Am J Phys Med Rehabil Assoc Acad Physiatr 2006, 85(11):S15-28. quiz S29–31
• [4]Zink A, Listing J, Kary S, Ramlau P, Stoyanova-Scholz M, Babinsky K, et al.: Treatment continuation in patients receiving biological agents or conventional DMARD therapy. Ann Rheum Dis 2005, 64:1274-9.
• [5]Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, et al.: Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 2002, 46:1443-50.
• [6]Das UN: Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essent Fatty Acids 2000, 63:351-62.
• [7]Cleland LG, James MJ: Fish oil and rheumatoid arthritis: antiinflammatory and collateral health benefits. J Rheumatol 2000, 27:2305-7.
• [8]Roush JK, Dodd CE, Fritsch DA, Allen TA, Jewell DE, Schoenherr WD, et al.: 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.
• [9]Wann AKT, Mistry J, Blain EJ, Michael-Titus AT, Knight MM: Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation. Arthritis Res Ther 2010, 12:R207. BioMed Central Full Text
• [10]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 Soc Exp Biol Med N Y N 2000, 223:88-95.
• [11]Humphries JM, Kuliwaba JS, Gibson RJ, Fazzalari NL: In situ fatty acid profile of femoral cancellous subchondral bone in osteoarthritic and fragility fracture females: implications for bone remodelling. Bone 2012, 51:218-23.
• [12]Moreau M, Troncy E, Del Castillo JRE, Bédard C, Gauvin D, Lussier B: Effects of feeding a high omega-3 fatty acids diet in dogs with naturally occurring osteoarthritis. J Anim Physiol Anim Nutr 2013, 5:830-7.
• [13]Knott L, Avery NC, Hollander AP, Tarlton JF: Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease. Osteoarthr Cartil OARS Osteoarthr Res Soc 2011, 19:1150-7.
• [14]Genevois J-P, Autefage A, Fayolle P, Cazieux A, Leprieur Y: Traitement de l’arthrose chez le chien avec un polymère d’acide gras (ARA 3000 BETA N.D.). Point Vét 1985, 17:262-3.
• [15]Baugé C, Legendre F, Leclercq S, Elissalde JM, Pujol JP, Galéra P, et al.: Interleukin-1β impairment of transforming growth factor β1 signaling by down-regulation of transforming growth factor β receptor type II and up-regulation of Smad7 in human articular chondrocytes. Arthritis Rheum 2007, 56:3020-32.
• [16]Baugé C, Beauchef G, Leclercq S, Kim SJ, Pujol JP, Galéra P, et al.: NFκB mediates IL-1β-induced down-regulation of TβRII through the modulation of Sp3 expression. J Cell Mol Med 2008, 12:1754-66.
• [17]Duval E, Bigot N, Hervieu M, Kou I, Leclercq S, Galéra P, et al.: Asporin expression is highly regulated in human chondrocytes. Mol Med Camb Mass 2011, 17:816-23.
• [18]Bernadat D: Ara 3000beta - Action sur le cartilage. L’essentiel 2011, 216:20-1.
• [19]Paquet J, Goebel J-C, Delaunay C, Pinzano A, Grossin L, Cournil-Henrionnet C, et al.: Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators? Arthritis Res Ther 2012, 14:R60. BioMed Central Full Text
• [20]Grousson D, Moissonnier P, Tusseau C: Utilisation d’un polymère d’acides gras saturés et insaturés sodés (ARA 3000 BETA) dans le traitement symptomatique de la dysplasie de la hanche chez le chien. Pratique Médicale et Chirurgicale de l’Animal de Compagnie 1990, 2:159-66.
• [21]Calder PC: Fatty acids and inflammation: the cutting edge between food and pharma. Eur J Pharmacol 2011, 668(1):S50-8. [Pharma-Nutrition]