Leptin Receptor负向调控应力刺激诱导的后纵韧带骨化的分子机制及转化研究

Development of ossification of posterior longitudinal ligament (OPLL) is complex. It is not easy to prevent and treat OPLL. It is now believed that OPLL developed because of genetic factors and environmental factors. However, it has been rarely studied that how genetic factors and environmental factors work together. Some literature indicated that Lepr (Leptin receptor) signaling may play as a negative modulator of mechanosensitivity of ossification of posterior longitudinal ligament. It means that Leptin Receptor might play an important role between the genetic factors and environmental factors (as mechanical stress). The purpose of this project is to prove this hypothesis by in vitro and in vivo experiment. And this result would combine the study of genetic factors with the study of environmental factors. Moreover, it will make us getting better understanding of the mechanisam of OPLL. And it will help us to develop better diagnosis and treatment methods for OPLL.

后纵韧带骨化症（OPLL）是由遗传因素和环境因素（如机械应力）共同作用引起的复杂病变。其预防和治疗都是较棘手的问题。然而对于遗传因素与机械应力是如何相互作用，引起OPLL 的发生，仍然缺乏研究。研究表明Leptin Receptor（瘦素受体）介导的信号通路可能在机械应力刺激引起的OPLL的 发生、发展中起负向调控作用；故Leptin Receptor信号通路可能是外因（机械应力）和内因（基因因素）相互作用的一个关联点。本项目拟通过细胞学试验、动物体内试验等多个方面来验证Leptin Receptor通路在OPLL 发生中所起的作用和机制。若在这个层面取得进展，则可将遗传学研究和环境因素研究结合起来，可以以更宽的视角和更深的层面了解疾病的发生发展，并且可为早期诊断甚至发现特异性治疗方法打下较好的理论基础。