Mineral-Matrix Relations in Calcifying Tissues

钙化组织中的矿物质-基质关系

• 批准号: 6625728
• 负责人: WILLIAM J LANDIS
• 金额: $ 34.31万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625728
• 关键词: athymic mouse; atomic force microscopy; bone sialoprotein; calcification; collagen; extracellular matrix proteins; in situ hybridization; infrared spectrometry; intermolecular interaction; laboratory mouse; laser capture microdissection; limb bone; minerals; molecular dynamics; normal ossification; osteocalcin; osteopontin; tendons; tissue /cell culture; tissue engineering; transmission electron microscopy; turkeys

DESCRIPTION (provided by applicant): The major goal of this proposal is to obtain new information concerning the process of vertebrate skeletal mineralization at the molecular and cellular level. An understanding of mineralization is significant because it is the foundation for mechanical support of the body, for skeletal adaptation under mechanical constraint, as an ion reservoir, and for treating, preventing, and curing a variety of skeletal abnormalities that affect human well being. The proposed study will focus on three model systems, the calcifying tendon from normal turkeys, long bone from exercised mice, and a tissue-engineered model of phalanges and small joints. These systems will be examined under natural conditions and after changes that alter mechanical forces acting on them. A combination of molecular biological, biochemical, immunochemical, and structural techniques will be used to determine the processes by which cells elaborate an organic matrix that mineralizes, as well as the chemical and structural nature of matrix-mineral interaction. The specific hypothesis to be examined is: the structural and functional adaptation of a calcifying tissue to mechanical perturbation is directed by expression of osteopontin (opn), osteocalcin (oc) and bone sialoprotein (bsp), and their interactions with mineral deposition. The Specific Aims that will probe this structure-function relationship are to (1) establish the expression pattern of the selected genes (opn, oc, bsp) as compared to specific matrix proteins, matrix receptors, cytoskeletal proteins and mineral formation in the three model systems; (2) determine the adaptive response at the tissue level in terms of these parameters following perturbation of the tendon model altered by a surgically-induced mechanical change, and of the bone model through exercise; and (3) assess the adaptive response at the organ level by determining the pattern of protein expression and protein-mineral interactions in the phalanx-joint model placed under a muscular load. This multifaceted approach will contribute to an increased understanding of the chemistry, structure, organization, and interactions of relevant molecules and cells that are critically important for the function of mineralizing tissues and their adaptation under mechanical loading.

描述（由申请人提供）：该提案的主要目标是 获得有关脊椎动物骨骼过程的新信息 分子和细胞水平的矿化。的理解 矿化作用很重要，因为它是机械的基础 身体的支撑，用于机械约束下的骨骼适应，作为 离子储库，用于治疗、预防和治愈各种骨骼疾病 影响人类福祉的异常现象。拟议的研究将重点关注 三个模型系统，正常火鸡的钙化肌腱，来自火鸡的长骨 运动小鼠，以及指骨和小关节的组织工程模型。 这些系统将在自然条件下和经过改变后进行检查 改变作用在它们上的机械力。分子生物学的结合， 生物化学、免疫化学和结构技术将用于 确定细胞形成有机基质的过程 矿化以及基质矿物的化学和结构性质 相互作用。要检验的具体假设是：结构和 钙化组织对机械扰动的功能适应是 由骨桥蛋白 (opn)、骨钙素 (oc) 和骨的表达指导 唾液酸蛋白（bsp）及其与矿物质沉积的相互作用。这 探究这种结构-功能关系的具体目标是 (1) 将所选基因（opn、oc、bsp）的表达模式建立为 与特定基质蛋白、基质受体、细胞骨架蛋白相比 以及三个模型系统中的矿物形成； (2) 确定自适应 根据以下这些参数在组织水平上的反应 通过手术引起的机械作用改变肌腱模型的扰动 通过锻炼改变骨骼模型； (3) 评估适应性 通过确定蛋白质表达模式在器官水平做出反应 以及置于 a 下的指骨关节模型中的蛋白质-矿物质相互作用 肌肉负荷。这种多方面的方法将有助于提高 了解化学、结构、组织和相互作用 对功能至关重要的相关分子和细胞 矿化组织及其在机械负荷下的适应。