Water‐soluble C60 fullerene prevents degeneration of articular cartilage in osteoarthritis via down‐regulation of chondrocyte catabolic activity and inhibition of cartilage degeneration during disease development

• Published in: Arthritis and rheumatism Vol. 56; no. 10; pp. 3307 - 3318
• Main Authors: Yudoh, Kazuo, Shishido, Kiyoshi, Murayama, Hideki, Yano, Mitsunobu, Matsubayashi, Kenji, Takada, Hiroya, Nakamura, Hiroshi, Masuko, Kayo, Kato, Tomohiro, Nishioka, Kusuki
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2007; Wiley
• Subjects: Adjuvants, Immunologic - pharmacology; Aged; Aged, 80 and over; Animals; Apoptosis - drug effects; Biological and medical sciences; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cells, Cultured; Cellular Senescence - drug effects; Chondrocytes - drug effects; Chondrocytes - metabolism; Disease Models, Animal; Disease Progression; Diseases of the osteoarticular system; Down-Regulation; Free Radical Scavengers - pharmacology; Fullerenes - pharmacology; Humans; Hyaluronic Acid - pharmacology; In Vitro Techniques; Medical sciences; Miscellaneous. Osteoarticular involvement in other diseases; Osteoarthritis; Osteoarthritis, Knee - metabolism; Osteoarthritis, Knee - therapy; Oxidative Stress - drug effects; Rabbits; Disease development; Water; Knee; Ligament; Oxidative stress; Left; Chondrocyte; Pathogenesis; Diseases of the osteoarticular system; Right; Ethylene oxide polymer; Intraarticular administration; Degenerative disease; Degeneration; Semilunar cartilage; Human; Interleukin 1β; Joint; Treatment; Articular cartilage; Animal; Interleukin 10; Arthropathy; Bone; Osteoarthritis
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.22917

Objective Studies have shown the roles of oxidative stress in the pathogenesis of osteoarthritis (OA) and induction of chondrocyte senescence during OA progression. The aim of this study was to examine the potential of a strong free‐radical scavenger, water‐soluble fullerene (C60), as a protective agent against catabolic stress–induced degeneration of articular cartilage in OA, both in vitro and in vivo. Methods In the presence or absence of C60 (100 μM), human chondrocytes were incubated with interleukin‐1β (10 ng/ml) or H2O2 (100 μM), and chondrocyte activity was analyzed. An animal model of OA was produced in rabbits by resection of the medial meniscus and medial collateral ligament. Rabbits were divided into 5 subgroups: sham operation or treatment with C60 at 0.1 μM, 1 μM, 10 μM, or 40 μM. The left knee joint was injected intraarticularly with water‐soluble C60 (2 ml), while, as a control, the right knee joint received 50% polyethylene glycol (2 ml), once weekly for 4 weeks or 8 weeks. Knee bone and cartilage tissue were prepared for histologic analysis. In addition, in the OA rabbit model, the effect of C60 (10 μM) on degeneration of articular cartilage was compared with that of sodium hyaluronate (HA) (5 mg/ml). Results C60 (100 μM) inhibited the catabolic stress–induced production of matrix‐degrading enzymes (matrix metalloproteinases 1, 3, and 13), down‐regulation of matrix production, and apoptosis and premature senescence in human chondrocytes in vitro. In rabbits with OA, treatment with water‐soluble C60 significantly reduced articular cartilage degeneration, whereas control knee joints showed progression of cartilage degeneration with time. This inhibitory effect was dose dependent, and was superior to that of HA. Combined treatment with C60 and HA yielded a significant reduction in cartilage degeneration compared with either treatment alone. Conclusion The results indicate that C60 fullerene is a potential therapeutic agent for the protection of articular cartilage against progression of OA.