Abstrato

Polyhydroxylated C60 fullerenes prevent chondrocyte catabolic activity at nanomolar concentrations in osteoarthritis

Hirotaka Yoshioka, Naoko Yui, Kanaka Yatabe, Hiroto Fujiya, Haruki Musha, Hisateru Niki, Rie Karasawa & Kazuo Yudoh

Aim: Recently, numerous reports have demonstrated that oxidative stress and related chondrocyte aging may participate in the development of osteoarthritis (OA). To further understand the pathogenesis and degenerative process of OA, we have studied water-soluble polyhydroxylated C60 fullerene, a strong free radical scavenger, as an anti-oxidant. Method: We examine the therapeutic effects of five types of water-soluble polyhydroxylated C60 fullerenes [C60(OH)10, C60(OH)24, C60(OH)26, C60(OH)36, C60(OH)44] on OA-related factor-induced catabolic responses in osteoarthritic chondrocytes. In the presence or absence of polyhydroxylated C60 fullerenes [C60(OH)10, C60(OH)24, C60(OH)26, C60(OH)36, C60(OH)44] (0.1, 1.0, 10.0 or 100 nM), human osteoarthritic chondrocytes were treated with IL-1β (10.0 ng/mL). After 24 hours incubation, chondrocyte activities were examined. Results: Water-soluble polyhydroxylated C60 fullerenes inhibited OA-related catabolic responses (IL-1β- upregulation of cartilage degrading enzyme production and downregulation of proteoglycan production) in OA chondrocytes. C60(OH)10 C60(OH)24 and C60(OH)26 showed a stronger chondroprotective effect than C60(OH)36 or C60(OH)44. Conclusion: Our findings indicate that polyhydroxylated C60 fullerenes, especially C60(OH)10 C60(OH)24 and C60(OH)26, may have a part to protect against OA related factor-mediated downregulation of osteoarthritic chondrocyte activities. These data may reveal a novel pathologic mechanism linking oxidative stress-induced development of OA.