Regeneration of the Developing Chick Elbow Joint

描述(由申请人提供)：发育中的小鸡肘关节项目摘要：组成肘关节、膝盖和髋关节的滑膜关节对于日常生活中的功能非常重要。先天性缺陷、疾病和滑膜关节的创伤，特别是组成关节的关节软骨，正在使数十亿人虚弱。由于缺乏完全的关节置换术，使关节恢复到NORML功能状态的治疗方法非常缺乏。阻碍临床措施进展的是关节软骨固有的修复或再生能力。因此，在进行接缝修复之前 要测试和利用以再生为基础的程序，即再生医学，必须了解构成关节的组织的再生过程。然而，到目前为止，还没有一项关于滑膜关节再生的研究。P.I.开发了一种联合再生的模式，并对其进行了表征。利用胚胎雏鸡模型，P.I.发现假定的肘关节在移除后能够再生，这种能力随后会随着发育年龄的增加而丧失。组织学和分子分析表明，关节的再生遵循一个发展程序(重新开发)。我们还发现成纤维细胞生长因子(成纤维细胞生长因子)能够在非再生模型中诱导再生。利用组织学、细胞标记、显微镜、增殖分析、RT-PCR和原位杂交，P.I.将在基因表达模式的背景下分析再生、细胞迁移和增殖的初始阶段。了解负责再生的细胞的遗传和行为特征，应该使我们能够开始了解启动再生的要求。再生的后期，即形态发生，将使用显微CT扫描和组织学进行仔细分析。使用成纤维细胞生长因子诱导再生的特点是确定再生所需的关键上游和下游因素及其在这一过程中发挥的具体作用。这个项目的长期目标是阐明再生组成关节的组织所需的因素，包括肌肉、骨骼和软骨。这些特定的目的是为了描述再生的初始和后期阶段以及成纤维细胞生长因子诱导的再生反应。这项工作将为肢体再生和再生医学领域奠定具有重要意义的基础。 与公共健康相关：在大多数人的一生中，在某个时候，关节的完整性会因为创伤、疾病、衰老或先天缺陷而减少。这项提案中概述的研究使用了关节再生的第一个模型，以开始揭示肢体组织启动关节再生所必需的线索。通过研究这一过程，研究人员将更接近于实现人类的再生修复。

DESCRIPTION (provided by applicant): Regeneration of the Developing Chick Elbow Joint Project Summary Synovial joints such as those that comprise the elbow, knee, and hip are extremely important for functioning in everyday life. Congenital defects, disease and trauma to synovial joints, in particular to the articular cartilage that comprises a joint, are debilitating o billions of people. Short of total joint replacement, therapies to bring the joint back to its norml functioning condition are sorely lacking. Impeding the progress of clinical measures is the inherent inability of articular cartilage to repair or regenerate itself. Thus, before joint repair procedures based on regeneration, i.e. regenerative medicine, are to be tested and utilized, there must be an understanding of the regeneration process of the tissues that comprise a joint. Until now, however, there has not been a study focused on regeneration of a synovial joint. The P.I. has developed and characterized a model of joint regeneration. Using the embryonic chick model, the P.I. has found that the presumptive elbow joint is able to regenerate following removal, and this ability is subsequently lost with increasing developmental age. Histological and molecular analyses have shown that regeneration of the joint follows a developmental program (redevelopment). We have also found that fibroblast growth factor (FGF) is able to induce regeneration in a non-regenerative model. Using histology, cell labeling, microscopy, proliferation assays, RT- PCR and in situ hybridization, the P.I. will analyze the initial stages o regeneration, cell migration and proliferation, in the context of gene expression patterns. Knowing the genetic and behavioral profile of the cells responsible for regeneration should enable us to begin to understand the requirements for regeneration to be initiated. The late stage of regeneration, morphogenesis, will be carefully analyzed using microCT scanning and histology. The induction of regeneration using FGF will be characterized with the goal of identifying critical upstream and downstream factors necessary for regeneration and the specific roles they play in the process. The long-term goal of this project is to elucidate the factors required to regenerate the tissues that make up a joint, including muscle, bone, and cartilage. The specific aims are designed to characterize the initial and later stages of regeneration as well as the FGF-induced regeneration response. This work will lay a foundation that will have significant implications in the fields of limb regeneration and regenerative medicine. PUBLIC HEALTH RELEVANCE: At some point in most everyone's life, joint integrity will be diminished either through trauma, disease, aging, or congenital defects. The research outlined in this proposal uses the first model of joint regeneration to begin to uncover the cues that are necessary for the tissues of the limb to initiate regeneration of a joint. By studying this process investigators will be that much closer to achieving regenerative repair in humans.