Mineral-Matrix Relations in Calcifying Tissues

描述（由申请人提供）：本提案的主要目标是 获得有关脊椎动物骨骼发育过程的新信息 在分子和细胞水平上的矿化。了解 矿化是重要的，因为它是机械的基础。 支撑身体，在机械约束下骨骼适应，如 离子库，并用于治疗，预防和治愈各种骨骼 影响人类健康的异常现象拟议的研究将集中于 三个模型系统，来自正常火鸡的钙化肌腱，来自 运动的小鼠，以及一个组织工程化的趾骨和小关节模型。 这些系统将在自然条件下进行检查， 改变作用于它们的机械力。结合了分子生物学， 生物化学、免疫化学和结构技术将用于 决定细胞制造有机基质的过程， 以及基质矿物的化学和结构性质 互动要检验的具体假设是： 钙化组织对机械扰动的功能适应 通过骨桥蛋白（OPN）、骨钙素（OC）和骨 唾液蛋白（BSP）及其与矿物质沉积相互作用。的 探索这种结构-功能关系的具体目的是（1） 建立所选基因（OPN、OC、BSP）的表达模式， 与特定的基质蛋白、基质受体、细胞骨架蛋白相比， （2）确定了三个模型系统的适应性 根据以下参数，组织水平的响应 由应力引起的机械扰动改变的肌腱模型的扰动 改变，和骨模型通过运动;和（3）评估适应性 通过确定蛋白质表达模式在器官水平的反应 和蛋白质-矿物质相互作用的指骨关节模型下， 肌肉负荷这一多方面的办法将有助于加强 了解化学，结构，组织和相互作用， 相关的分子和细胞，是至关重要的功能， 矿化组织及其在机械负荷下的适应。

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.