Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Inhibitory effects of ZSTK474, a novel phosphoinositide 3-kinase inhibitor, on osteoclasts and collagen-induced arthritis in mice. | Toyama et al. Arthritis Research Therapy 2010 12 R92 http content 12 3 R92 RESEARCH ARTICLE Open Access Inhibitory effects of ZSTK474 a novel phosphoinositide 3-kinase inhibitor on osteoclasts and collagen-induced arthritis in mice Shoko Toyama 1 Naoto Tamura 1 Kazuhiko Haruta2 Takeo Karakida3 Shigeyuki Mori2 Tetsuo Watanabe2 Takao Yamori4 and Yoshinari Takasaki1 Abstract Introduction Targeting joint destruction induced by osteoclasts OCs is critical for management of patients with rheumatoid arthritis RA . Since phosphoinositide 3-kinase PI3-K plays a critical role in osteoclastogenesis and bone resorption we examined the effects of ZSTK474 a novel phosphoinositide 3-kinase PI3-K -specific inhibitor on murine OCs in vitro and in vivo. Methods The inhibitory effect of ZSTK474 on OC formation was determined and compared with other PI3-K inhibitors by counting tartrate-resistant acid phosphatase TRAP -positive multinucleated cells after culturing murine bone marrow monocytic OC precursors and cells. Activation of Akt and expression of nuclear factor of activated T cells NFAT c1 in cultured cells were examined. The suppressing effect of ZSTK474 on bone resorption was assessed by the pit formation assay. The in vivo effects of ZSTK474 were studied in collagen-induced arthritis CIA in the mouse. Oral daily administration of ZSTK474 was started either when more than half or when all mice developed arthritis. Effects of ZSTK474 were evaluated using the arthritis score and histological score of the hind paws. Results ZSTK474 inhibited the differentiation of bone marrow OC precursors and cells in a dose-dependent manner. The inhibitory effect of ZSTK474 was much stronger than that of LY294002 the most commonly used PI3-K inhibitor. In addition ZSTK474 suppressed the bone resorbing activity of mature OCs. Moreover oral daily administration of ZSTK474 even when begun after the development of arthritis ameliorated CIA in mice .
