冲击力作用下种植体周围骨组织与骨结合界面损伤特征及其功能性改建过程中sclerostin作用机制研究

Dental implant may suffer from impact load in the process of sports, physical training which would cause the microdamage of alveolar bone around the dental implant. The remodling of alveolar bone would be affected by the bite force under this condition. The mechanism of damage and repair of alveolar bone around implant due to bite force on implant is still unclear. The osseointegration between the surfaces of the implant and bone is a fundamental prerequisite for implant to maintain its stability and support the bite force. The alveolar bone remodeling is induced by the mechanical regulation factor and bring about the bone formation or bone loss which would affect the success of dental implant. There have been some reports that sclerostin has close relation with mechanical signal path of Wnt (bone formation) and RANKL (bone loss). But the effect of sclerostin on the process of microdamage and remodeling of alveolar bone around implant is still unclear. Analysis of the correlation between microdamage of alveolar bone around implant due to impact load and the expression of sclerostin is the key to this problem. In order to achieve these objectives, the animal model with implant under impact force will be established. Micro-CT, scanning electron microscope, histological staining, Western Blot and qRT-PCR are used to study the characteristic of microdamage and the expression of sclerostin/Wnt and sclerostin/RANKL, in order to reveal the mechanism of damage and repair of alveolar bone around implant due to impact load and bite force. The results could be used to evaluate the influence of impact load on the alveolar bone trauma around implant, and help to promote the remodeling of it in clinical dental practice.

种植义齿在运动、训练等活动时所承受的冲击载荷易导致种植体周围骨组织和骨结合界面出现损伤，在咬合力作用下还会出现不同形式的骨改建，但其机制尚不清楚。力学敏感因子sclerostin被认为是参与调控Wnt（成骨）和RANKL（破骨）通路的关键分子，课题组研究发现冲击损伤后骨组织中sclerostin表达出现改变，并可能会在咬合力的诱导下参与骨改建。因此，分析骨组织损伤特征，阐明咬合力是如何通过sclerostin来影响损伤后骨改建，这是研究冲击损伤和修复的关键问题。本项目拟建立种植体周围骨组织冲击损伤动物模型；采用Micro-CT、扫描电镜、组织学研究，分析骨组织损伤特征与载荷冲量的关系；应用Western Blot和qRT-PCR测定sclerostin、β-catenin、RANKL在损伤和改建过程中的表达变化。通过上述研究揭示骨组织冲击损伤和修复机制，为临床冲击损伤评估和治疗提供依据。

随着种植技术的发展与种植修复的普及，种植义齿承受外部瞬态冲击力作用的情况也快速增加。在许多突发事件如交通事故、体育竞赛、士兵训练、地质灾害、军事冲突等状况下，种植义齿会承受类似天然牙外伤的冲击载荷，从而导致种植体周围骨组织和骨结合界面出现损伤，在咬合力作用下还会出现不同形式的骨改建，但冲击力作用下种植体周围骨组织损伤特征与咬合力对损伤后种植义齿的影响还未见研究和报道。本研究在前期研究的基础上，1. 建立冲击载荷作用下种植体周围骨组织损伤动物模型和数值模拟分析模型，分析种植体周围骨组织和骨结合界面冲击损伤过程和损伤特征。2. 采用Micro-CT、扫描电镜、组织学研究揭示冲击载荷和咬合力加载与骨组织和骨结合界面损伤的相关关系。3. 应用Western Blot和qRT-PCR测定冲击损伤后和咬合力诱导下力学敏感因子sclerostin和参与调控Wnt（成骨）和RANKL（破骨）通路的关键分子表达变化及其对骨组织改建过程的影响，揭示冲击载荷作用下种植体周围骨损伤与修复机制。研究发现：1. 冲击载荷易造成种植体周围骨组织微结构的损伤，冲击力会以应力波的形式在种植体和骨组织结合界面间传播和反射，从而形成对骨组织和骨结合的“二次破坏”。2. 冲击加载后，种植体稳定性下降，种植体颈部皮质骨凹陷，种植体骨结合界面局部区域出现界面脱开、骨结合破坏，周围骨小梁发生断裂，骨组织微结构发生改变，损伤程度与冲击载荷大小呈正相关。3. 冲击损伤后咬合力刺激加重骨吸收，减慢骨形成，不利于冲击损伤后种植体-骨结合界面恢复和骨组织微结构愈合。4. 种植体周围骨组织在损伤和改建中，sclerostin通过调控Wnt/β-catenin通路和RANK-RANKL通路影响骨改建过程。研究结果表明临床上种植体冲击损伤的患者应结合病史进行全面的检查和评估，合理调整咬合力，防止其松动、脱落。通过上述研究揭示了骨组织冲击损伤和修复机制，为临床冲击损伤评估和治疗提供依据。