TYPE X COLLAGEN IN LIMB DEVELOPMENT

X 型胶原蛋白在四肢发育中的作用

• 批准号: 3448262
• 负责人: THOMAS M SCHMID
• 金额: $ 5.31万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448262
• 关键词: bone development; bone metabolism; cartilage development; cartilage metabolism; chondrocytes; collagenase; early embryonic stage; extracellular matrix; gel electrophoresis; histochemistry /cytochemistry; histogenesis; hydroxyapatites; hypertrophy; immunochemistry; immunofluorescence technique; limbs; mammalian embryology; microscopy; normal ossification; osteogenesis; tissue /cell culture

Long bones form the major supportive structures of limbs. The ossified tissue first develops around and finally within a cartilage primordium. The maturation of embryonic long bones is dependent on the synchronous transition from cartilage to bone. The long term goal of this project is to understand the cellular regulation of endochondral bone formation. The process may be conveniently studied in the epiphyseal growth plate where the cellular changes occur as a linear continuum. The chondrocytes pass through several stages typified by high mitotic activity or high levels of macromolecular synthesis. Finally, the cells hypertrophy and are replaced by osteogenic cells. Recently, a short collagen molecule, termed type X collagen, has been shown to be a specific product of the hypertrophic chondrocytes. The aims of this study will be to examine the structural function of type X collagen during the formation of endochondral bone. The temporal and spatial distribution of the molecule have been determined by immunohistochemical methods and suggest type X collagen may be involved in the turnover or calcification of the hypertrophic cartilage matrix. The possible role of the molecule in the turnover of the matrix will be assessed by first quantitating the ratio of type X to type II collagen in the matrix. Second, the rates of a mammalian collagenase degradation of types X and II will be compared. Third, hypertrophic cartilage will be analyzed for the presence of enzymes capable of degrading type X collagen. The potential function of the molecule in the calcification of tissue will also be examined. First, the histological distribution of hydroxyapatite will be compared with the location of type X by immunohistochemistry. Second, intramembranous bone will be analyzed biochemically for the presence of type X collagen which has been detected in the tissue by indirect immonufluoresence.

长骨形成了四肢的主要支撑结构。 骨化 组织首先在软骨原基周围发展，最后发展。 胚胎长骨的成熟取决于同步 从软骨到骨骼的过渡。 这个项目的长期目标是 了解内软骨骨形成的细胞调节。 这 可以方便地研究过程中的过程 细胞变化作为线性连续体发生。 软骨细胞通过 通过高丝分裂活性或高水平的几个阶段 大分子合成。 最后，细胞肥大并被替换 通过成骨细胞。 最近，一个短胶原分子称为X型 胶原蛋白已被证明是肥厚的特定产物 软骨细胞。 这项研究的目的是检查结构 X型胶原蛋白的功能在内侧软骨骨的形成过程中。 这 分子的时间和空间分布已确定 免疫组织化学方法并建议X型胶原蛋白可能参与 肥厚软骨基质的周转或钙化。 这 该分子在基质营业额中的可能作用将是 通过首先定量X型与II型胶原蛋白的比率进行评估 矩阵。 其次，哺乳动物胶原酶降解的速率 将比较X型和II型。 第三，肥厚的软骨将是 分析了能够降解X型胶原蛋白的酶的存在。 该分子在组织钙化中的潜在功能将 也可以检查。 首先，羟基磷灰石的组织学分布 通过免疫组织化学将与X型的位置进行比较。 其次，将对膜内骨进行生化分析 X型胶原蛋白的存在已在组织中检测到 间接侵蚀。