基于中药选择性Cathepsin K活性的抑制剂对骨质疏松的分子机制研究

骨质疏松症已成为中国进入人口老龄化的社会健康问题，而且也成为医疗健康系统的主要负担。目前中国有8600万骨质疏松患者，到2050年患者人数将达到1.8亿。破骨细胞中Cathepsin K 的胶原蛋白酶活性过高是促进骨(Bone)和软骨(Cartilage)组织等处骨基质和骨软骨胶原蛋白的过多降解的主要原因。制药公司投入了巨大财力来研发骨吸收抑制剂。前期研究工作表明，丹参和地黄的提取物中均含有选择性抑制Cathepsin K活性的成分。本课题研究拟利用胶原降解法和荧光法筛选骨吸收抑制剂；拟利用肌动蛋白形成能力试验、胶原吸收实验、细胞迁移实验、破骨细胞能力实验和骨消化实验等研究骨吸收抑制对骨质疏松细胞模型的作用；拟利用去卵巢骨质疏松模型小鼠研究骨吸收抑制剂的作用机理，以期为研究和发展治疗骨骼类新药奠定基础。

Osteoporosis is a major health problem in the aging populations of China. Currently, there are 86 million of osteopororis patiens in China. And this number will increase to 180 million in 2050. The major pathological mechanism is that the collagenlytic activity of cathepsin K has been abnormal high surrounding bone and cartilage. And the pharmaceutical companys has invested huge money on develop anti-resorptive inhibitors.The previous experiments revealed that the extracts from Danshen and Dihuang can seletive inhibiting the activity of Cathepsin K. In this project, collagenlytic methods and fluorescence polarization will be employed to sreen anti-resorptive inhibitors. The mathods that F-actin ring formation, osteoclast pit formation, cell transmigration, osteoclast activity and bone digestion will be employed to study the effects of anti-resorptive inhibitors on osteoporosis cell models. And also ovariectomied mice will be employed to study the mechanisms of anti-resorptive inhibitors.These studies will offer the foundations for the development of new drugs to treat skeletal diseases.