BONE GENERATION AND REGENERATION

该项目的长期目标是了解 骨生成和再生的机制。在调查期间 软骨基质分子参与牙槽骨修复， 短型IX型胶原的时间表达是 在拔牙的早期愈合阶段， 套接字.两种不同启动子在大肠杆菌中的交替选择 （α-l（IX）基因可以产生长IX型胶原，其被转录 从上游启动子含有一个大的氨基末端小球，和 从下游启动子转录的短IX型胶原 完全省略了小球。短IX型的空间定位 拔牙窝中的胶原蛋白主要存在于 相对无组织的基质和活跃形成的骨小梁。 α-1（IX）“敲除”转基因小鼠的拔牙窝显示， 骨骼修复迟缓和紊乱因此。我们假设 短IX型胶原可能在牙槽骨中具有重要作用 修复和可能在任何骨形成过程中。成员的 FACIT类基质分子，IX型胶原修饰表面 II型胶原纤维，从而为组织提供了 特定的分子间相互作用We.因此，假设 IX型胶原蛋白分子的异质性， 启动子的选择可能与以下基因的差异表达密切相关： 软骨和骨表型。 本申请书提出的项目的具体目标是：1） 为了研究短IX型胶原在骨形成过程中的作用， 2）了解组织特异性的分子机制 选择α-l（IX）基因中的替代启动子。达成 这些目标，我们建议完成分析的时间和 牙槽骨中II型和IX型胶原空间表达 修复以及胚胎骨形成期间。我们将应用 分子生物学和免疫鉴定技术。具体 短IX型胶原在牙槽骨修复过程中的作用将是 在具有失活（“敲除”）α-1的转基因小鼠中研究 (XI)等位基因此外，α-半乳糖苷酶的替代启动子区也是一个新的启动子区。 I（IX）基因将被彻底表征。的调控机制 通过报告基因测定来解决选择性转录， 迁移率变动分析和DNA足迹分析。这些研究结果 研究将提供对骨生成的进一步了解， 再生，以及骨愈合的基本先决条件 伤口

The long-term goal of the proposed project is to understand the molecular mechanisms of bone generation and regeneration. During investigations of the involvement of cartilage matrix molecules in alveolar bone repair, the temporal expression of the short form of type IX collagen was demonstrated during the early healing stages of the tooth extraction socket. The alternative selection of two distinct promoters in the (alpha-1(IX) gene can generate long type IX collagen that is transcribed from the upstream promoter contains a large amino-terminal globule, and short type IX collagen that is transcribed from the downstream promoter completely omits the globule. The spatial localization of short type IX collagen in the tooth extraction socket was found mostly in the relatively unorganized matrix and the actively forming bone trabeculae. The extraction socket of alpha-1(IX) "knock-out" transgenic mice showed retarded and disorganized bone repair. Therefore. we hypothesize that short type IX collagen may have a significant role in alveolar bone repair and possibly in any bone formation processes. As a member of the FACIT class of matrix molecules, type Ix collagen decorates the surface of type II collagen fibrils and thus provides the site for tissue specific molecular interactions. We. therefore. hypothesize that heterogeneity in type IX collagen molecules due to the alternative promoter selection may be closely related to differential expressions of cartilage and bone phenotypes. The specific goals of the projects proposed in this application are: 1) to investigate the role of short type IX collagen during bone formation, and 2) to understand the molecular mechanism of the tissue specific selection of the alternative promoters in the alpha-1 (IX) gene. To reach these goals, we propose to complete the analysis of the temporal and spatial expression of type II and IX collagens during alveolar bone repair as well as during embryonic bone formation. We will apply molecular biologic and immuno-identification techniques. The specific role of short type IX collagen during alveolar bone repair will be investigated in transgenic mice with inactivated ("knock-out") alpha-1 (XI) alleles. Furthermore, the alternative promoter regions of the alpha- l(IX) gene will be thoroughly characterized. The regulatory mechanism of the alternative transcription will be addressed by reporter gene assay, mobility shift assay and DNA foot printing assay. The findings from these studies will provide further understanding of bone generation and regeneration, and the essential prerequisites for sound healing of bone wounds.