Kikuta Junichi, Shirazaki Mai, Sudo Takao, Mizuno Hiroki, Morimoto Akito, Suehara Riko, Minoshima Masafumi, Kikuchi Kazuya, Ishii Masaru
Department of Immunology and Cell Biology Graduate School of Medicine and Frontier Biosciences Osaka University 2-2 Yamada-oka Suita Osaka 565-0871 Japan.
Department of Material and Life Science Graduate School of Engineering Osaka University 2-1 Yamada-oka Suita Osaka 565-0871 Japan.
JBMR Plus. 2018 Jun 22;2(6):362-366. doi: 10.1002/jbm4.10057. eCollection 2018 Nov.
Bisphosphonates are commonly used for the treatment of bone disorders such as osteoporosis; however, the mechanism by which they affect the dynamics of living mature osteoclasts in vivo remains unknown. Here, we describe the short-term effects of different bisphosphonates on controlling the bone resorptive activity of mature osteoclasts in living bone tissues of mice using intravital two-photon microscopy with a pH-sensing chemical fluorescent probe. Three types of nitrogen-containing bisphosphonates, risedronate, alendronate, and minodronate, inhibited osteoclastic acidification during osteoporotic conditions just 12 hours after i.v. injection. Among the three types of drugs, risedronate was the most effective at increasing osteoclast motility and changing the localization of proton pumps, which led to an inhibition of bone resorption. Together, these results demonstrate that the intravital imaging system is a useful tool for evaluating the similarities and differences in currently used antibone resorptive drugs. © 2018 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
双膦酸盐常用于治疗骨质疏松症等骨骼疾病；然而，它们在体内影响活的成熟破骨细胞动力学的机制仍不清楚。在此，我们使用带有pH传感化学荧光探针的活体双光子显微镜，描述了不同双膦酸盐对控制小鼠活骨组织中成熟破骨细胞骨吸收活性的短期影响。三种含氮双膦酸盐，利塞膦酸盐、阿仑膦酸盐和米诺膦酸盐，在静脉注射后仅12小时就在骨质疏松条件下抑制了破骨细胞的酸化。在这三种药物中，利塞膦酸盐在增加破骨细胞运动性和改变质子泵定位方面最有效，这导致了骨吸收的抑制。总之，这些结果表明，活体成像系统是评估目前使用的抗骨吸收药物异同的有用工具。© 2018作者。由Wiley Periodicals, Inc.代表美国骨与矿物质研究学会出版。
