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.

长骨构成了四肢的主要支撑结构。僵化的人 组织首先在软骨原基周围发育，最后在软骨原基内发育。 胚胎长骨的成熟依赖于同步性 从软骨到骨骼的过渡。这个项目的长期目标是 了解软骨内骨形成的细胞调控。这个 可以方便地在骨痂生长板中研究过程，其中 细胞的变化以线性连续体的形式发生。软骨细胞传代 经过几个阶段，以高有丝分裂活动或高水平的 大分子合成。最后，细胞肥大并被取代 通过成骨细胞。最近，一种名为X型的短胶原分子 胶原蛋白，已被证明是肥厚性疾病的一种特定产物 软骨细胞。这项研究的目的将是检查结构 X型胶原在软骨内骨形成中的作用这个 分子的时间和空间分布由 免疫组织化学方法并提示X型胶原可能参与了 肥大的软骨基质的周转或钙化。这个 分子在基质周转中的可能作用将是 通过首先量化X型和II型胶原的比率来评估 矩阵。第二，哺乳动物胶原酶的降解率 将比较类型X和类型II。第三，肥大的软骨将 分析是否存在能够降解X型胶原的酶。 分子在组织钙化中的潜在功能将 也要接受检查。第一，羟基磷灰石的组织分布 将其与免疫组织化学方法定位的X型进行比较。 其次，膜内骨将进行生化分析，以确定 在组织中检测到的X型胶原的存在 间接免疫荧光。