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Avocado/Soybean Unsaponifiables Increase Aggrecan Synthesis and Reduce Catabolic and Proinflammatory Mediator Production by Human Osteoarthritic Chondrocytes
YVES E. HENROTIN, CHRISTELLE SANCHEZ, MICHELLE A. DEBERG, NATHALIE PICCARDI, GEORGES BERNARD GUILLOU, PHILIPPE MSIKA, and JEAN-YVES L. REGINSTER
ABSTRACT.
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 1ß (IL-1ß). 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-1ß (MIP-1ß), 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 µg/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-1ß treatment. A1S2 was a potent inhibitor of basal and IL-1ß stimulated MMP-3 production. The procedure also weakly reversed the inhibitory effect of IL-1ß on TIMP-1 production. A1S2 inhibited basal production of MIP-1ß, 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-1ß 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. (J Rheumatol 2003;30:1825-34) Key Indexing Terms:
AVOCADO From the Bone and Cartilage Metabolism Research Unit, University Hospital, CHU Sart-Tilman, Liège, Belgium. Supported by a grant from Laboratoires Expanscience, Courbevoie, France. C. Sanchez was supported as a pre-doctoral fellow by Belgian FNRS. Y.E. Henrotin, PhD; C. Sanchez, BSc; M.A. Deberg, PhD, Bone and Cartilage Metabolism Research Unit, University Hospital, Liège; N. Piccardi, PhD; G.B. Guillou, MD; P. Msika, PhD, Laboratoires Expanscience, Courbevoie, France; J-Y.L. Reginster, MD, PhD, Bone and Cartilage Metabolism Research Unit, University Hospital, CHU Sart-Tilman, Liège. Address reprint requests to Dr. Y. Henrotin, Bone and Cartilage Metabolism Research Unit, Institute of Pathology, CHU Bat B23, B-4000 Liège, Belgium. E-mail: yhenrotin@ulg.ac.be Submitted May 30, 2002; revision accepted January 30, 2003. |