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Avocado/Soybean Unsaponifiables Prevent the Inhibitory Effect of Osteoarthritic Subchondral Osteoblasts on Aggrecan and Type II Collagen Synthesis by Chondrocytes
YVES E. HENROTIN, MICHELLE A. DEBERG, JEAN-MICHEL CRIELAARD, NATHALIE PICCARDI, PHILIPPE MSIKA, and CHRISTELLE SANCHEZ ABSTRACT. Objective. To determine the effects of avocado/soybean unsaponifiables (ASU) on osteoblast-induced dysregulation of chondrocyte metabolism. Methods. Human chondrocytes were isolated from osteoarthritis (OA) cartilage and cultured in alginate beads for 4 or 10 days in the absence or presence of osteoblasts isolated from nonsclerotic (NSC) or sclerotic (SC) zones of OA subchondral bone plate in monolayer. Before co-culture, osteoblasts were incubated or not with 10 µg/ml ASU for 72 hours. Aggrecan, type II collagen, matrix metalloproteinase-3 (MMP-3) and MMP-13, tissue inhibitor of metalloproteinase (TIMP-1), transforming growth factor-ß1 (TGF-ß1) and TGF-ß3, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA levels in chondrocytes were quantified by RT-PCR. Aggrecan, osteocalcin, TGF-ß1, interleukin 1ß (IL-1ß), and IL-6 production were assayed by immunoassays. Results. In co-culture, SC osteoblasts induced a significant inhibition of matrix protein production and a significant increase of MMP synthesis by chondrocytes. In contrast, SC osteoblasts did not modify TIMP-1, TGF-ß1 and TGF-ß3, iNOS, or COX-2 mRNA levels in chondrocytes. The pretreatment of SC osteoblasts with ASU fully prevented the inhibitory effects of SC osteoblasts on matrix component production, and even significantly increased type II collagen mRNA level over the control (chondrocytes alone) value. In contrast, pretreatment of SC osteoblasts with ASU did not significantly modify the expression of MMP, TIMP-1, TGF-ß1, TGF-ß3, iNOS, or COX-2 gene by chondrocytes. Conclusion. ASU prevent the osteoarthritic osteoblast-induced inhibition of matrix molecule production, suggesting that this compound may promote OA cartilage repair by acting on subchondral bone osteoblasts. This finding constitutes a new mechanism of action for this compound, known for its beneficial effects on cartilage. (First Release July 1 2006; J Rheumatol 2006;33:1668–78) Key Indexing Terms:
OSTEOARTHRITIS From the Bone and Cartilage Metabolism Research Unit, Institute of Pathology B23; Centre for Oxygen Research and Development, CHU Sart-Tilman; and Centre for Immunology, CHU Sart-Tilman, University of Liège, Liège, Belgium; and Laboratoires Expanscience, Epernon, France. Supported in part by Expanscience and Belgian FNRS grants. C. Sanchez was supported as a pre-doctoral fellow by Belgian FNRS. Y.E. Henrotin, PhD, Professor, Bone and Cartilage Metabolism Research Unit, Institute of Pathology B23; Centre for Oxygen Research and Development, CHU Sart-Tilman; and Centre for Immunology, CHU Sart-Tilman, University of Liège; M.A. Deberg, PhD; J-M. Crielaard, MD, PhD, Professor, Bone and Cartilage Metabolism Research Unit, Institute of Pathology B23, University of Liège; N. Piccardi, PhD; P. Msika, PhD, Laboratoires Expanscience; C. Sanchez, PhD, Bone and Cartilage Metabolism Research Unit, Institute of Pathology B23, University of Liège. Address reprint requests to Dr. Y.E. Henrotin, Bone and Cartilage Research Unit, Institute of Pathology, CHU Sart-Tilman, 4000 Liège, Belgium. E-mail: yhenrotin@ulg.ac.be. Accepted for publication March 15, 2006.
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