Lactoferrin在大鼠腭中缝发育及牵张成骨中的调控机理研究

Suture distraction osteogenesis(SDO) is one of the important technologies in orthodontic-orthopaedic treatment. Orthodontists and orthopedic surgeons try to find efficient methods to improve the results, shortten the period and prevent the relapse of the treatment. Lactoferrin(LF) has extensive biologocal effects in human body, and has been found that it can motivate the proliferation and differentiation of osteoblasts, suppress apoptosis, as well as inhibit the formation of osteoclasts, which in all decrease bone resorption. Local injection of lactoferrin could promote mineraliztion and formation of bone in the original region. The aim of this study is to explore the effect and mechanism of LF in rat midpalatal suture development and the remodeling process in SDO induced by mechanical stress. In this study, we are going to use Micro-CT, MTT, FMC, RT-PCR, HE, Masson ,IHC and other detection methods to investigate 1)the expression of LF、LRP1、p42/44 MAPK、p38 MAPK、RANKL/OPG in growing rat midpalatal suture and the regulation mechanism of the cells in suture,2)the effects and regulation of lactoferrin on remodeling of the suture in vivo，3）the effects and regulation of lactoferrin on proliferation、 differentiation、apoptosis of chondrocytes and osteoblasts subjected to mechanical strain in vitro. The results of this study may offer more information for understanding the effects and molecular mechanisms of lactoferrin in suture development，as well as in suture distraction osteogenesis, and provide better insights into improving its therapeutic effect on bone formation.

骨缝牵张成骨是牙颌畸形矫形治疗的重要技术。探寻有效方法促进骨缝处新骨的形成从而提高矫形效果、缩短疗程和防止复发一直是学者们关注的热点。乳铁蛋白(Lactoferrin）在人体内具有广泛而重要的生物学作用。研究发现其能有效地刺激成骨细胞的增殖和分化，抑制其凋亡，同时抑制破骨细胞的形成，从而减少骨吸收的发生。 本课题拟通过观察大鼠腭中缝发育及牵张成骨不同阶段，腭中缝组织和细胞乳铁蛋白、LRP1、p42/44 MAPK、p38 MAPK、RANKL/OPG等信号分子的表达规律，分析乳铁蛋白在骨缝塑建及改建中的作用和机制。同时通过乳铁蛋白介导下的成骨细胞、软骨细胞以及体内骨缝组织应力加载实验，观察外源性乳铁蛋白对应力刺激下细胞增殖分化凋亡的影响以及骨缝牵张成骨区域新骨形成情况，从而进一步揭示乳铁蛋白对骨缝牵张过程中机械应力效应细胞的调控机制及其对骨缝牵张成骨效应的影响。

骨缝牵张成骨（suture distraction osteogenesis，SDO）是临床上改善颌骨骨量和骨形态比较常用的一种手段。SDO的作用机制及如何提高牵张成骨的效率，稳定治疗后的效果，防止复发是当前研究热点。. 本项目利用外源性乳铁蛋白（Lactoferrin，LF），通过建立腭中缝牵张（即上颌快速扩弓，Rapid palatal expansion，RPE）及复发动物实验模型、体外细胞机械应力加载模型，研究LF对于腭中缝牵张及复发效应的影响和可能的作用机制。结果发现外源性LF可以通过增强腭中缝骨改建过程中的成骨活动、抑制破骨活动增加上颌扩弓的稳定性、减少复发量，其效果与不同干预方式及剂量呈相关性。在此过程中，LF促进了成骨细胞的成骨标志物的表达增加。同时，LF对于骨缝牵张成骨的影响可能通过MAPK以及OPG/RANKL/RANK信号通路发挥作用的。. 本项目研究结果展示了大鼠腭中缝生长发育规律，探索了LF对于腭中缝牵张中骨缝改建的影响效应和可能作用机制，为LF作为促进上颌扩弓的稳定性、减少复发量的有效干预措施的临床应用提供了理论依据。