广泛流行在贵州省的地方性氟中毒（简称地氟病）是持续列入我国“十二五”和“健康中国2020行动计划”的重点防治疾病，该病虽然病因清楚，但致病机制未明，严重危害居民健康，影响经济社会发展，是我省亟待解决的重大公共卫生问题。本项目在既往研究发现氟暴露上调CyclinD1和CDK4转录与表达基础上，利用miRNA芯片技术，结合生物信息学分析，在燃煤污染型地方性氟中毒人群中筛选并验证靶向调控CyclinD1/CDK4的miRNA。同时构建人原代成骨细胞氟中毒模型，过表达和抑制相关miRNA，展开相关miRNA靶向调控CyclinD1/CDK4的机制研究，进而揭示其对氟所致成骨细胞增殖活跃的影响。在既往DNA甲基化和组蛋白乙酰化研究基础上，继续从表观遗传学的miRNA调控角度展开系统研究，探索氟骨症发生机制，为地方性氟中毒防治提供新的科学依据。

The endemic fluorosis, which is widely prevalent in Guizhou province, has been consecutively listed in our country’s “Twelfth Five-year Plan” and “Healthy China 2020” Strategic Plan as an important prevented disease. The pathogeny of endemic has been found out, however, the pathogenesis is not clear, which threatens people’s health and hinders the development of economy and society. The endemic fluorosis has become a public concern which needs to be solved promptly. This research is based on the findings in our previous studies that fluoride can upregulate expression of CyclinD1 and CDK4 mRNA and protein. This research makes full use of miRNA microarray technology and bioinformatics analysis to screen and verify miRNA targeting CyclinD1 / CDK4 in population with endemic fluorosis induced by coal-burning. This research also establishs an in vitro model of fluorosis with human primary osteoblasts by overexpression and suppression related miRNA, and conducts research of mechanism of related miRNA regulation by targeting CyclinD1 / CDK4. Its purpose is to reavle the effects of related miRNA in actively proliferating osteoblasts induced by fluoride. This research tries to explore skeletal fluorosis mechanism systematically with miRNA perspective in epigenetics based on DNA methylation and histone acetylation, and then to provide new scientific evidence for the prevention and therapy of fluorosis.