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Mineral-Matrix Relations in Calcifying Tissues

钙化组织中的矿物质-基质关系

基本信息

批准号：
7053352
负责人：
WILLIAM J LANDIS
金额：
$ 30.83万
依托单位：
NORTHEAST OHIO MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-05-01 至 2009-03-31
项目状态：
已结题

项目摘要

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)：本提案的主要目标是获取有关脊椎动物骨骼过程的新信息分子和细胞水平的矿化作用。一种对矿化意义重大，因为它是机械化的基础身体的支撑，用于在机械约束下的骨骼适应，如离子蓄水器，用于治疗、预防和治疗各种骨骼疾病影响人类福祉的异常现象。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，来自训练小鼠，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在发生变化后进行检查改变作用在它们上面的机械力。结合了分子生物学，将使用生化、免疫化学和结构技术来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互动。需要检验的具体假设是：结构性和钙化组织对机械扰动的功能适应是骨桥蛋白(OPN)、骨钙素(Oc)和骨的表达唾液蛋白(BSP)及其与矿物沉积的相互作用。这个探讨这种结构-功能关系的具体目的是(1) 建立所选基因(opn、oc、bsp)的表达模式为与特定的基质蛋白、基质受体、细胞骨架蛋白相比以及三个模型体系中的成矿作用；(2)确定根据以下这些参数在组织水平上的响应由手术诱导的机械改变的肌腱模型的扰动通过运动改变骨骼模型；以及(3)评估适应性通过确定蛋白质表达模式在器官水平上的反应和蛋白质-矿物相互作用的指骨-关节模型放置在一个肌肉负荷。这种多方面的方法将有助于提高对化学、结构、组织和相互作用的理解对细胞的功能至关重要的相关分子和细胞矿化组织及其在机械载荷下的适应性。

项目成果

期刊论文数量（37）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Analysis of human osteoarthritic connective tissue by laser capture microdissection and QRT-PCR.

通过激光捕获显微切割和 QRT-PCR 分析人类骨关节炎结缔组织。

DOI：
10.1080/03008200701692685
发表时间：
2007
期刊：
Connective tissue research
影响因子：
2.9
作者：
Scharschmidt,Thomas;Jacquet,Robin;Laskovski,Jovan;Lowder,Elizabeth;Weiner,Scott;Landis,WilliamJ
通讯作者：
Landis,WilliamJ

Tissue-engineered meniscal constructs.

组织工程半月板结构。