Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes
[en] OBJECTIVE: To investigate the effects of avocado (A)/soybean (S) unsaponifiables on the metabolism of human osteoarthritic (OA) chondrocytes cultured in alginate beads over 12 days. METHODS: Enzymatically isolated OA chondrocytes were cultured in alginate beads in a well defined culture medium for 12 days, in the presence or not of 10-10 M interleukin 1beta (IL-1beta). DNA content was measured using a fluorometric method. Production of aggrecan (AGG), stromelysin-1 (MMP-3), tissue inhibitor of metalloproteinases-1 (TIMP-1), macrophage inflammatory protein-1beta (MIP-1beta), IL-6, and IL-8 were assayed by specific enzyme amplified sensitivity immunoassays. Prostaglandin (PG) E2 was measured by a specific radioimmunoassay and nitrite by a spectrophotometric method based on the Griess reaction. A commercial avocado and soybean mixture of unsaponifiables (A1S2) and each component separately were tested in a range of 0.625 to 40.0 micro g/ml. RESULTS: After 12 days' incubation, A1S2 increased AGG synthesis and accumulation in alginate beads in a dose and time dependent manner. A1S2 promoted the recovery of aggrecan synthesis after 3 days of IL-1beta treatment. A1S2 was a potent inhibitor of basal and IL-1beta stimulated MMP-3 production. The procedure also weakly reversed the inhibitory effect of IL-1beta on TIMP-1 production. A1S2 inhibited basal production of MIP-1beta, IL-6, IL-8, NO*, and PGE2 by OA chondrocytes and partially counteracted the stimulating effect of IL-1 on PGE2. Compared to avocado or soybean added separately, the mixture had a superior effect on NO* and IL-8 production. CONCLUSION: A1S2 stimulated aggrecan production and restored aggrecan production after IL-1beta treatment. In parallel, A1S2 decreased MMP-3 production and stimulated TIMP-1 production. These results suggest A1S2 could have structure-modifying effects in OA by inhibiting cartilage degradation and promoting cartilage repair.
Disciplines :
Rheumatology
Author, co-author :
Henrotin, Yves ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) - Didactique des sciences de la santé - Pathologie générale et physiopathologie
Sanchez, Christelle ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Deberg, Michelle ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Piccardi, Nathalie
Guillou, Georges Bernard
Msika, Philippe
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Language :
English
Title :
Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes
Braunstein EM, Brandt KD, Albrecht M. MRI demonstration of hypertrophic articular cartilage repair in osteoarthritis. Skeletal Radiol 1990;19:335-9.
Brandt KD, Braunstein EM, Visco DM, O'Connor B, Heck D, Albrecht M. Anterior (cranial) cruciate ligament transection in the dog: a bona fide model of canine osteoarthritis, not merely of cartilage injury and repair. J Rheumatol 1991;18:436-46.
Vignon E, Arlot M, Hartmann D, Moyen B, Ville G. Hypertrophic repair of articular cartilage in experimental osteoarthrosis. Ann Rheum Dis 1983;42:82-8.
Martel-Pelletier J, Zafarullah M, Kodama S, Pelletier JP. In vitro effects of interleukin 1 on the synthesis of metalloproteases, TIMP, plasminogen activators and inhibitors in human articular cartilage. J Rheumatol 1991;18 Suppl 27:80-4.
Moldovan F, Pelletier JP, Hambor J, Cloutier JM, Martel-Pelletier J. Collagenase-3 (matrix metalloproteinase 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum 1997;40:1653-61.
Fernandes JC, Martel-Pelletier J, Lascau-Coman V, et al. Collagenase-1 and collagenase-3 synthesis in early experimental osteoarthritic canine cartilage. An immunohistochemical study. J Rheumatol 1998;25:1585-94.
Sandy JD, Flannery CR, Neame PJ, Lohmander LS. The structure of aggrecan fragments in human synovial fluid. Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the GLU 373-Ala 374 bond of the interglobular domain. J Clin Invest 1992;89:1512-16.
Okada Y, Shimnei M, Tanaka O, et al. Localization of matrix metalloproteinase-3 (stromelysin) in osteoarthritic cartilage and synovium. Lab Invest 1992;66:680-90.
Nguyen Q, Mort JS, Roughley PJ. Preferential mRNA expression of prostromelysin relative to procollagenases and in situ localization in human articular cartilage. J Clin Invest 1992;89:1189-97.
Mohtai M, Smith RL, Schurman DJ, et al. Expression of 92-KD type IV collagenase/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin-1. J Clin Invest 1993;92:179-85.
Walter H, Kawashim A, Nebelung W, Neumann W, Roessner A. Immunohistochemical analysis of several proteolytic enzymes as parameters of cartilage degradation. Pathol Res Pract 1998;194:73-81.
Towle C, Hung H, Bonassar L, Treadwell B, Mangham D. Detection of interleukin-1 in cartilage of patients with osteoarthritis: possible autocrine/paracrine role in pathogenesis. Osteoarthritis Cartilage 1997;5:293-300.
Pelletier JP, Faure MP, Di Battista JA, Wilhelm S, Visco D, Martel-Pelletier J. Co-ordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study. Am J Pathol 1993;142:95-105.
Tetlow LC, Adam DJ, Wooley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage. Arthritis Rheum 2001;44:585-94.
Bocquet J, Daireaux M, Langris M, et al. Effect of interleukin-1-like factor (mononuclear cell factor) on proteoglycan synthesis in cultured human articular chondrocytes. Biochem Biophys Res Commun 1986;134:539-49.
Pujol JP, Brisset M, Jourdan C, et al. Effects of a monocyte cell factor on collagen production by cultured articular chondrocytes: role of prostaglandin E2. Biochem Biophys Res Commun 1984;119:499-508.
Henrotin Y, De Groote D, Labasse A, et al. Effects of exogenous IL-1β, TNFα, IL-6, IL-8 and LIF on cytokine production by human chondrocytes. Osteoarthritis Cartilage 1996;4:163-73.
Borzi RM, Mazzetti I, Cattini L, Uguccioni M, Bagglioni M, Facchini A. Human chondrocytes express functional chemokine receptors and release matrix-degradating enzymes in response to C-X-C and C-C chemokines. Arthritis Rheum 2000;43:1743-51.
Tiku K, Liesch JB, Robertson FM. Production of hydrogen peroxide by rabbit articular chondrocytes. Enhancement by cytokines. J Immunol 1990;145:690-6.
Blotman F, Maheu E, Wulwik A, Gaspard H. Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip: a prospective, multicenter, three months, randomized, double blind, placebo controlled trial. Rev Rhum Engl Ed 1997;64:825-34.
Maheu E, Mazière B, Valat J-P, al. Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six months treatment period and a two months follow-up demonstrating a persistent effect. Arthritis Rheum 1998;41:81-91.
Appelboom T, Schuermans J, Verbruggen G, Henrotin Y. Reginster J-Y. Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis. Scand J Rheumatol 2001;30:242-7.
Lequesne M, Maheu E, Cadet C, Dreiser RL. Structural effects of avocado/soya unsaponifiables (ASU) on joint space loss in osteoarthritis of the hip. Arthritis Rheum 2002;47:50-8.
Cake MA, Read RA, Guillou B, Ghosh P. Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables. Osteoarthritis Cartilage 2000;8:404-11.
Boumediene K, Felisaz N, Bogdanowicz P, Galera P, Guillou B, Pujol J-P. Avocado/soya unsaponifiables enhance the expression of transforming growth factor β1 and β2 in cultured articular chondrocytes. Arthritis Rheum 1999;42:148-56.
Henrotin Y, Labasse AH, Jaspar JM, et al. Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 production by human articular chondrocytes. Clin Rheumatol 1998;17:31-9.
Sanchez C, Mateus M, Defresne M-P, Crielaard J-M, Reginster J-Y, Henrotin Y. Metabolism of human chondrocytes cultured in alginate beads. Longterm effects of interleukin 1β and nonsteroidal antiinflammatory drugs. J Rheumatol 2002;29:772-82.
Zheng SX, Mouithys-Mickalad A, Deby-Dupont GP, al. In vitro study of the antioxidant properties of nimesulide and 4-OH nimesulide: effects on HRP- and luminol-dependent chemiluminescence produced by human chondrocytes. Osteoarthritis Cartilage 2000;8:419-25.
Labarca C, Paigen K. A simple, rapid and sensitive DNA assay procedure. Anal Biochem 1980;102:344-52.
Serteyn D, Deby-Dupont G, Pincemail J, Mottart E, Philippart C, Lamy M. Equine postanaesthetic myositis: thromboxanes, prostacyclin and prostaglandin E2 production. Vet Res Commun 1988;12:219-26.
Green L, Wagner D, Glogowski J, Skipper P, Wishnok J, Tannenbaum S. Analysis of nitrate, nitrite, and (15N) nitrate in biological fluids. Anal Biochem 1982;126:131-8.
Woessner JF Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 1991;5:2145-54.
Kuettner KE, Thonar EJM. Osteoarthritis and related disorders: cartilage integrity and homeostasis. In: Klippel JH, Dieppe PA, editors. Rheumatology. 2nd ed. London: Mosby International; 1998:861-16.
Murphy G, Cocket MI, Stephens PE, Smith BJ, Doherty AJ. Stromelysin is an activator of procollagenase: a study with natural and recombinant enzymes. Biochem J 1987;248:265-8.
Van Osch GJVM, van den Berg WB, Hunziker EB, Hauselmann HJ. Differential effects of IGF-1 and TGF-β2 on the assembly of proteoglycans in pericellular and territorial matrix by cultured bovine articular chondrocytes. Osteoarthritis Cartilage 1998;6:187-95.
Lindlad S, Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum 1987;30:1081-8.
Koch AE, Kunkel SL, Shah MR, et al. Macrophage inflammatory protein-1β: A C-C chemokine in osteoarthritis. Clin Rheumatol 1995;77:307-14.
Borzi RM, Mazzetti I, Macor S, et al. Flow cytometric analysis of intracellular chemokines in chondrocytes in vivo: constitutive expression and enhancement in osteoarthritis and rheumatoid arthritis. FEBS Lett 1999;455:238-42.
Kerbel B, Clergeau-Guerithault S, Brion M. A scanning electron microscope study of experimental periodontal disease. Its induction and inhibition. J Periodontol 1975;46:27-35.
Guerne PA, Desgeorges A, Jaspar JM, Relic B, Hoffmeyer P, Dayer JM. Effects of IL-6 and its soluble receptor on proteoglycan synthesis and NO release by human articular chondrocytes: comparison with IL-1. Modulation by dexamethasone. Matrix Biol 1999;18:253-60.
Jikko A, Wakisaka T, Iwamoto M, al. Effects of interleukin-6 on proliferation and proteoglycan metabolism in articular chondrocyte cultures. Cell Biol Int 1998;22:615-22.
Flannery CR, Little CB, Hughes CE, Curtis CL, Caterson B, Jones SA. IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Matrix Biol 2000;19:549-53.
Rowan AD, Koshi PJ, Shingleton WD, et al. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum 2001;44:1620-32.
Murrell GAC, Jang D, Williams RJ. Nitric oxide activates metalloprotease enzymes in articular cartilage explants. Biochem Biophys Res Commun 1995;206:121-8.