Core--Morphology and biomechanics

描述（由申请人提供）： 骨关节炎的特点是渐进性变性的 关节软骨的关节，最终导致炎症，疼痛， 和行动不便。在本提案中，我们将讨论分子 骨关节炎的生物学，通过操纵体外软骨形成 细胞培养系统，基因敲入技术的应用， 然后表征表达突变形式的软骨II型和IX型的小鼠， 和软骨寡聚基质蛋白（COMP），并鉴定候选物 参与软骨发育和成熟的基因， 基因表达谱形态学/生物力学核心的目标 (Core领导者：洛基S。Tuan）将提供最先进的设施， 用于表征形态、结构、基因 细胞和组织的表达谱分析和机械性能测试 从计划项目的研究项目中产生。形态 核心的组成部分，将负责日常工作 组织学、免疫组织化学、原位杂交、超微结构和 共聚焦激光扫描显微镜，并将在骨科进行 托马斯杰斐逊大学研究实验室。生物力学组件 将由机械工程系的洛里塞顿博士监督 在杜克大学，并将负责应用渗透 载荷技术，以确定关节的力学性能 在实验小鼠模型中， 基因突变核心的两个组成部分都由经验丰富的 研究者在应用方面具有既定的、已发表的经验， 这些技术在软骨细胞和组织中。形态学/生物力学 因此，Core在软骨的终点分析中起着重要作用 结构和功能，是成功完成 每个研究项目中提出的研究。

DESCRIPTION (provided by applicant): Osteoarthritis is characterized by the progressive degeneration of the articular cartilage of the joints, ultimately leading to inflammation, pain, and impairment of mobility. In this proposal, we will address the molecular biology of osteoarthritis by means of manipulation of an in vitro chondrogenic cell culture system, application of gene knock-in technology to generate and then characterize mice that express mutated forms of cartilage types II and IX, and cartilage oligomeric matrix protein (COMP), and identification of candidate genes involved in cartilage development and maturation by means of differential gene expression profiling. The objective of the Morphology/Biomechanics Core (Core Leader: Rocky S. Tuan) is to provide state-of-the-art facilities and technologies for the characterization of the morphological, structural, gene expression profiling, and mechanical property testing of the cells and tissues generated from the Research Projects of the Program Project. The Morphology Component of the Core, will be responsible for routine histology, immunohistochemistry, in situ hybridization, ultrastructure, and confocal laser scanning microscopy, and will be carried out at the Orthopaedic Research Laboratory at Thomas Jefferson University. The Biomechanics Component will be supervised by Dr. Lori Setton in the Mechanical Engineering Department at Duke University, and will be responsible for the application of the osmotic loading technique to determine the mechanical properties of joint articular cartilage in the experimental mouse models that harbor the extracellular matrix gene mutations. Both Components of the core are staffed by experienced investigators with established, published experience in the application of these techniques in cartilage cells and tissues. The Morphology/Biomechanics Core therefore serves a vital function in the end-point analysis of cartilage structure and function, and is essential for the successful completion of the studies proposed in each of the Research Projects.