我国不仅地氟病危害严重，工业性氟病引起的骨损伤亦较明显。氟性骨损伤是长期摄入过量氟引起机体骨组织广泛性骨质增生硬化的慢性骨代谢病，特征性病变为高骨转换状态。最新研究发现，破骨细胞通过Sema4D/PlexinB1通路来调节成骨细胞的分化成熟，成骨细胞又通过RANKL/RANK/OPG系统来调节破骨细胞的增殖分化。氟对这一调控环路的作用是氟性骨损伤发生发展过程中的主导环节。本项目采用细胞培养、动物实验及现场分子流行病学的方法，以氟阻滞Sema4D/Plexin-B1通路抑制成骨功能为核心，以氟性骨损伤早期损伤与防御为主线，阐明成骨抑制蛋白/骨转换状态/氟性骨损伤之间的关联性，解析氟阻滞Sema4D/Plexin-B1通路抑制成骨功能在氟性骨损伤中的作用及机制。为氟性骨损伤的有效干预提出新思路与手段，为制定科学合理的氟危害防治策略提供理论依据。

Not only can endemic fluorosis cause serious harm, but industrial fluorosis can cause obvious bone damage in China. Long-term exposure to high concentrations of fluoride can cause fluoride bone injury, including the increased density of the effected bone and the growth of new abnormal bone at ligament and tendon insertion sites. The pathological characteristic of this disease can be explained as increased osteoblast and osteoclast activity with high bone turnover. Emerging data suggest that osteoclasts can suppress osteogenesis function through Sema4D/PlexinB1 signaling pathway and osteoblasts mediate the differentiation of osteoclasts through the RANKL/RANK/OPG system. However, few studies focus on the change of the regulating loop caused by fluoride. We use the modern analytical chemistry, biology technology and molecular epidemiological methods, study the inhibition effect on Sema4D/Plexin-B1 signaling pathway by fluoride and explain the relationships among the inhibiting proteins of osteogenesis and the transition state of bone and fluoride bone injury in this project. Through the deepening research of these contents, we can put forward new ideas and means effectively for interventions of the early damage of fluoride bone injury and provide the theory basis for making a scientific and rational control strategy against fluorosis harm.

我国不仅地氟病危害严重，工业性氟病引起的骨损伤亦较明显。氟性骨损伤是长期摄入过量氟引起机体骨组织广泛性骨质增生硬化的慢性骨代谢病，特征病变为高骨转换。本项目采用细胞培养、动物实验及现场分子流行病学的方法，以Sema4D/PlexinB1调控成骨功能为核心，以氟性骨损伤早期损伤与防御为主线，从整体、细胞和分子水平阐明成骨抑制蛋白/骨转换状态/氟性骨损伤之间的关联性，解析氟阻滞Sema4D/PlexinB1蛋白通路抑制成骨功能在氟性骨损伤中的作用及机制。研究表明，在氟负荷下，Sema4D/PlexinB1蛋白表达受到抑制，对其信号通路的成骨抑制作用减弱，进而使前骨细胞向成骨细胞转化及数量增多、成骨功能增强，骨代谢呈高骨转化状态，最终导致氟性骨损伤的发生。Sema4D重组蛋白可抑制软骨细胞的增殖及X型胶原的表达，为防治氟危害提供了早期导向预防理论。