力学刺激对F-spondin成牙骨质作用的影响及机制初探

Root resorption with cementum destruction is an orthodontic clinical common complication, and the mechanism remains poorly understood. However, cementum destruction rarely happens in periapical periodontitis and periodontal disease which usually come with severe alveolar bone destruction. It hints that the orthodontic force and the special characters of cementum different from alveolar bone are two key points in orthodontic induced root resorption. F-spondin is found specifically located in cementoblasts and cementum.It might play an important role in cementum protection with the capability of inducing periodontal ligament cell differentiation to cementoblasts, and inhabitation migration and differentiation of cementoclast precursors.What is the role of F-spondin in cementum protection during orthodontic teeth movement is still unknown. Here our project will focus on F-spondin and cementum protection,designed to investigate the effect and the mechanism of F-spondin on cementoblastic differentiation of cementoblasts,observe the changes of F-spondin，the differentiation protein of cementoblasts and OPG/RANKL expression before and after different mechanical stimulus (light/heavy, tension/compression). We will study the relationship between mechanical stimulation and F-spondin which is important in cementoblastic differentiation of cementoblasts to reveal the mechanism. Finally we design orthodontic teeth movementanimal experiment to confirm the results from the study in vitro. Then it will reveal the relationships of " Mechanical stimulation - F - spondin - cementum"， make clear of effects of mechanical stimulation to F-spondin on cementoblastic differentiation of cementoblasts，and clarify mechanism of root remodeling during orthodontic treatment.

牙根吸收是正畸临床常见的并发症，而根尖周炎及牙周病时虽然牙槽骨发生严重的吸收破坏，牙根吸收却并不明显，说明牙根吸收与正畸力及牙骨质的组织特性密切相关。据文献回顾，F-spondin在成牙骨质细胞及牙骨质中特异性表达,可能对牙骨质新生具备双向调控作用。正畸牙移动时，力学刺激对F-spondin介导的成牙骨质作用有何影响？国内外尚无报道。本研究以F-spondin为切入点，观察不同大/小、加载形式（张/压）的力学刺激对成牙骨质细胞F-spondin的表达、成牙骨质细胞分化及OPG/RANKL表达的影响，采用基因转染技术及信号通道阻断剂研究力在F-spondin介导的成牙骨质中的作用及其信号传导途径，通过动物实验进一步探讨正畸力作用下F-spondin的牙骨质保护作用，揭示“力—F-spondin—牙骨质”三者的关系，进一步阐明正畸牙根吸收的发病机理，为临床牙根吸收防治提供理论依据及新思路。

牙根吸收是正畸牙移动的常见并发症，有趣的是根尖周炎及牙周病时虽然牙槽骨发生严重的吸收破坏，但牙根吸收却并不明显，说明牙根吸收与正畸力及牙骨质的组织特性密切相关。文献回顾提示F-spondin在成牙骨质细胞及牙骨质中特异性表达,可能对牙骨质新生具备双向调控作用。. 本研究以F-spondin为切入点，观察力学刺激对成牙骨质细胞分化的影响，研究F-spondin与成牙骨质细胞矿化的关系及机制，揭示“力—F-spondin—牙骨质”三者的关系，为进一步阐明正畸牙根吸收的发病机理，为临床牙根吸收防治提供理论依据及新思路。. 研究发现当张应变力学刺激强度从5%，10%到20%逐步增加时，成牙骨质细胞总凋亡率明显增加，说明重力会明显提高成牙骨质细胞的凋亡率，提示正畸临床合理使用矫治力有利于避免严重牙根吸收。进一步研究发现力学刺激影响成牙骨质细胞体外矿化，表现为加力后成牙骨质细胞F-spondin 、Runx2、ALP、COX2、RANKL及VEGF等mRNA的表达水平上调， OC、BSP及OPG等的mRNA表达水平下降，说明力学刺激虽然激活成牙骨质细胞成骨分化，促进细胞外基质成熟，但其终末成骨矿化能力有所下降。同时发现阻滞COX2信号通路可显著提高成牙骨质细胞矿化水平。本研究中力学刺激使成牙骨质细胞RANKL上调而OPG下调，结果RANKL/OPG比值升高，表明力学刺激成牙骨质样细胞可促进破骨细胞的分化和活化。探寻机制，研究发现阻滞剂XAV939使成牙骨质F-spondin、VEGF和COX2表达降低，说明Wnt信号通路参与F-spondin正向调节。阻滞剂实验说明成牙骨质细胞力学信号传递与Wnt 、NF-κB 、p38及COX2等多个信号通路有关。力学刺激下，成牙骨质细胞MAPK信号通路激活，Wnt及COX2信号通路表参与其中发挥调控作用。力学刺激上调F-spondin，F-spondin可促使FAK和ERK1/2磷酸化活化，说明F-spondin参与成牙骨质细胞成骨分化，通过ERK1/2、FAK，COX2等信号通路介导力学响应。本研究初步揭示了成牙骨质细胞力-F-spondin的关系及其力学信号转导机制，参与调控正畸牙根吸收，对揭示正畸牙根吸收的机制具有重要意义，有待深入探索。