Department of Frontier Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki City 216-8512, Japan.
Int J Nanomedicine. 2009;4:233-9. doi: 10.2147/ijn.s7505. Epub 2009 Oct 19.
Recently, it has been demonstrated that oxygen free radicals have an important role as a signaling messenger in the receptor activator NFkappaB (RANK) signal pathway required for osteoclast differentiation. 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 the RANK-induced osteoclastogenesis and osteoclastic bone destruction in arthritis, both in vitro and in vivo. The effects of C60 on the RANK-induced osteoclastogenesis and osteoclastic bone resorption were examined in vitro. Adjuvant-induced arthritic rats were used as an animal model of arthritis. Rats were divided into two subgroups: control and treatment with C60 at 1.0 microM. The left ankle joint was injected intra-articularly with water-soluble C60 (20 microl) in the C60-treated group, while, as a control, the left ankle joint in the control rats received phosphate-buffered saline (20 microl) once weekly for eight weeks. Ankle joint tissues were prepared for histologic analysis. C60 significantly inhibited the responses of osteoclast precursor cells to RANK ligand, including osteoclast differentiation and osteoclastic bone resorption in vitro. In adjuvant-induced arthritic rats, intra-articular treatment with C60 in vivo reduced the number of osteoclasts and alleviated bone resorption and destruction in the joints, while control ankle joints showed progression of joint destruction with time. These findings indicate that C60 downregulates the RANK-induced osteoclast differentiation and is a potential therapeutic agent for inhibition of osteoclastic bone destruction in arthritis.
最近的研究表明，氧自由基在核因子κB 受体激活剂（RANK）信号通路中作为一种信号信使，在破骨细胞分化中起着重要作用。本研究的目的是研究一种强自由基清除剂，水溶性富勒烯（C60），作为一种保护剂，防止 RANK 诱导的关节炎中的破骨细胞生成和破骨细胞性骨破坏，包括在体外和体内。C60 对 RANK 诱导的破骨细胞生成和破骨细胞性骨吸收的影响在体外进行了研究。采用佐剂诱导的关节炎大鼠作为关节炎的动物模型。大鼠分为两组：对照组和 C60 治疗组（1.0 μM）。在 C60 治疗组中，将水溶性 C60（20 μl）关节内注射到左踝关节中，而作为对照，在对照组大鼠的左踝关节中每周一次注射磷酸盐缓冲盐水（20 μl），共 8 周。制备踝关节组织进行组织学分析。C60 显著抑制破骨细胞前体细胞对 RANK 配体的反应，包括体外破骨细胞分化和破骨细胞性骨吸收。在佐剂诱导的关节炎大鼠中，体内关节内给予 C60 治疗减轻了关节中破骨细胞的数量，并缓解了骨吸收和破坏，而对照组踝关节随时间推移显示出关节破坏的进展。这些发现表明，C60 下调 RANK 诱导的破骨细胞分化，是一种抑制关节炎中破骨细胞性骨破坏的潜在治疗剂。
