牵张力对软骨细胞特异性Pkd1基因敲除后颅底软骨联合生长的影响及其机制研究

Synchondrosis is the growth center of cranial base, growth and development anomalies of cranial base synchondrosis are usaully caused by genetic defects and closely involved in the etiology of maxillo-facial deformity.The growth of synchondrosis is evidenced to be adaptive to tensile stress with active tissue reaction,but the potential corrective effect of tensile stress on the gene related growth anomalies of cranial base has still not been directly investigated. Polycystin-1,encoded by polycystic kidney disease 1 gene(Pkd1),is recently recognized as a new transmembrane protein that mediates mechanical signaling transduction; conditional Pkd1 gene deletion in certain tissue was found to cause deformity in related craniofacial region,but its mechanism is also unclear.Based on such a backgroud, the aims of this study are: (1)to establish an animal model of developmental synchondrosis deformity through chondrocyte-specific Pkd1 gene knockout in mouse; (2)to examine the effect of Pkd1 gene and tensile force on the growth of cranial base synchondrosis; (3)to investigate the cellular and molecular mechanisms of these two factors in the growth regulation of cranial base synchondrosis; and(4)to explore the difference and relationship between these two factors in the growth regulation of cranial base synchondrosis.The significance of this study includes further clarification of the different but related roles of genetic and mechanical factors in the growth of cranial base synchondrosis; better understanding of the linkage between the genetic etiology and mechanotherapeutic mechanisms in the maxillo-facial orthopedics.

颅底软骨联合是颅底的生长中心，其生长发育异常多因基因缺陷所致，并与颌面畸形的形成关系密切。力学刺激对正常颅底软骨联合生长具有明显促进作用，但能否弥补基因缺陷造成的生长异常？尚缺乏直接的实验依据。多囊性肾病1基因（ Pkd1 gene）编码的多囊蛋白1是一种近年来发现的具有力学信号转导功能的跨膜蛋白，条件性Pkd1基因敲除可导致小鼠颅面畸形，但其机理也尚不明确。基于上述研究背景，本研究拟通过小鼠软骨细胞特异性Pkd1基因敲除建立颅底发育畸形动物模型，明确Pkd1基因和牵张力两者在颅底软骨联合生长发育中的作用；从细胞和分子生物学层面分析和比较两者的作用效果和作用机制;通过对病因与力学矫治机理基础研究的整合，进一步揭示颅面畸形的基因学病因与力学矫治机理之间的联系，为完善颅面畸形的矫治策略提供理论依据。

颅底软骨联合是颅底的生长中心，其生长发育异常多因基因缺陷所致，并与颌面畸形的形成关系密切。力学刺激对正常颅底软骨联合生长具有明显促进作用，但能否弥补基因缺陷造成的生长异常尚缺乏直接的实验依据。多囊性肾病1基因（ Pkd1 gene）编码的多囊蛋白1（PC1）是一种具有力学信号转导功能的跨膜蛋白，条件性Pkd1基因敲除可导致小鼠颅面畸形，但其机理也尚不明确。本研究的结果显示，生长期小鼠蝶枕软骨联合表达 ＰＣ１，但不同生长阶段的表达区域和水平存在差异。长期牵张力刺激可促进包括颅底在内的小鼠颅面部骨组织纵向生长，延迟蝶枕软骨联合的骨化闭合。本研究资助的研究内容共发表文章2篇，其中一篇由SCI收录，1篇为中文核心期刊收录，资助培养博士研究生2名，硕士研究生1名，共申请发明专利1项，实用新型专利5项，资助完成1本学术专著出版。

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