颌面部骨骼疾病十型胶原蛋白基因的异常调控

项目名称： 颌面部骨骼疾病十型胶原蛋白基因的异常调控

项目编号： No.31271399

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 郑其平

作者单位： 江苏大学

项目金额： 70万元

中文摘要： 颌面部骨骼发育通常是通过间质细胞直接分化为骨细胞这一膜内成骨的方式进行。长骨或四肢骨干的发育则是以软骨细胞分化成熟即软骨内成骨的模式进行。膜内成骨受损可致多种颌面部骨骼畸变，占骨骼系统遗传病和出生缺陷的多数。临床表现为功能障碍或直接导致新生儿死亡。此外，许多颌面部综合症伴有长骨骨骼异常，现有资料也显示颌面部骨质细胞具有软骨细胞分化的属性，这些观察强烈提示软骨内成骨在颌面部骨骼疾病发生中起重要作用。然而，软骨内成骨如何参与颌面部骨骼疾病的发生迄今仍不清楚。基于长期对转录因子Runx2 和十型胶原蛋白基因Col10a1的研究，我们提出Runx2对Col10a1基因的调控异常是导致该类疾病发生的重要的病理基础。已知Runx2 和Col10a1 基因是软骨成熟的关键因素。进一步阐明Runx2 对Col10a1 基因的病理性调控与颌面部骨骼疾病发生发展的关联性，对于靶向治疗这一临床疾病具有重要意义

中文关键词： Col10a1与软骨细胞肥大；转录因子Runx2；：环氧化酶-2 Cox-2；转录因子Tbx5；LacZ转基因小鼠

英文摘要： The craniofacial skeleton usually develops through an intramembranous pathway in which mesenchymal cells directly differentiate into osteoblasts. The long bone development is though an endochondral pathway which requires a cartilage intermediate. Deficiency of intramembranous pathway results in many craniofacial skeletal anomalies. These craniofacial syndromes constitute a large group of congenital skeletal disorders that account for most of the skeletal birth defects. The clinical severity of these craniofacial syndromes ranges from minor handicap to death in neonatal period. Noticeably, many craniofacial skeletal disorders are accompanied by long bone abnormalities. There is also evidence that periosteal cells of craniofacial bones undergo chondrogenic differentiation. These observations strongly suggest that the endochondral pathway plays an important role in pathological occurrence of craniofacial skeletal diseases. However, until now, the mechanism by which the endochondral pathway causes craniofacial skeletal syndromes remains largely unknown. In this application, based on our series of research on Runx2 and Col10a1 (collagen X, alpha 1) genes, we propose that abnormal Col10a1 expression regulated by Runx2 constitutes a mechanistic basis of craniofacial skeletal disease. Both Runx2 and Col10a1 g

英文关键词： Col10a1 and chondrocyte hypertrophy；Transcription factor Runx2；Cox-2；Tbx5；LacZ transgenic mice