title: 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.
abstract: 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 microM), human chondrocytes were incubated with interleukin-1beta (10 ng/ml) or H2O2 (100 microM), 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 microM, 1 microM, 10 microM, or 40 microM. 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 microM) on degeneration of articular cartilage was compared with that of sodium hyaluronate (HA) (5 mg/ml).
  
  
  RESULTS
  C60 (100 microM) 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.
  
  
  CONCLUSIONS
  The results indicate that C60 fullerene is a potential therapeutic agent for the protection of articular cartilage against progression of OA.
authors: St. Marianna University School of Medicine, Kawasaki, Japan. yudo@marianna-u.ac.jp
authors: Kazuo
authors: K
authors: Yudoh
authors: Kiyoshi
authors: K
authors: Shishido
authors: Hideki
authors: H
authors: Murayama
authors: Mitsunobu
authors: M
authors: Yano
authors: Kenji
authors: K
authors: Matsubayashi
authors: Hiroya
authors: H
authors: Takada
authors: Hiroshi
authors: H
authors: Nakamura
authors: Kayo
authors: K
authors: Masuko
authors: Tomohiro
authors: T
authors: Kato
authors: Kusuki
authors: K
authors: Nishioka
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D037741:Fullerenes / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000628:therapy*; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits
chemical_list: D000276:Adjuvants, Immunologic; D016166:Free Radical Scavengers; D037741:Fullerenes; D006820:Hyaluronic Acid; C069837:fullerene C60