Regeneration of the Developing Chick Elbow Joint

发育中的雏鸡肘关节的再生

• 批准号: 7842434
• 负责人: Rosalie Anderson
• 金额: $ 0.5万
• 依托单位: LOYOLA UNIVERSITY IN NEW ORLEANS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7842434
• 关键词: Age; Aging; Animal Model; Animals; Back; Cartilage; Cells; Clinical; Congenital Abnormality; Data; Development; Disease; Elbow; Elbow joint structure; Elements; Embryo; Excision; Failure; Family; Fibroblast Growth Factor; Foundations; Gene Expression; Genes; Goals; Growth Factor; Healed; Hip region structure; Histology; Human; Joint repair; Joints; Knee; Knee joint; Label; Life; Limb structure; Measures; Mesenchymal; Microscopy; Modeling; Molecular; Morphogenesis; Muscle; Natural regeneration; Newts; Physical condensation; Procedures; Process; Proteoglycan; Radial; Rana; Regenerative Medicine; Replacement Arthroplasty; Replacement Therapy; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Salamander; Signal Transduction; Staging; Testing; Time; Tissues; Trauma; Vertebrates; Work; Zebrafish; aggrecan; articular cartilage; base; bone; chordin; design; gain of function; healing; humerus; inhibitor/antagonist; loss of function; member; novel; prospective; regenerative; repaired; response; skeletal; tissue processing; ulna

DESCRIPTION (provided by applicant): 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 to billions of people. Short of total joint replacement, therapies to bring the joint back to its normal 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 investigator proposes a model of joint regeneration and a novel means with which to study the regeneration process. Using the embryonic chick model, her preliminary data show that the presumptive elbow joint is able to regenerate following removal, and this ability is subsequently lost with increasing developmental age as evidenced by the lack of an elbow joint and what appear as cartilage fusions between elements. The proposed model of joint regeneration asserts that cells of the prospective skeletal elements that comprise the elbow, the humerus, radius, and ulna are first observed as continuous mesenchymal condensations. Genes associated with prechondrogenic or early condensations are observed. Subsequently, these genes are down regulated in the region of joint formation and genes regulating joint morphogenesis are expressed in the regenerating joint. The investigator' model purports that lack of joint morphogenetic signals during the healing process, results in limbs in which the skeletal elements are formed without an intervening elbow joint. In addition to this model of joint regeneration, she hypothesizes that the chick elbow is able to initiate regeneration following removal because of the presence and/or activation of a member(s) of the fibroblast growth factor (FGF) family. Based on studies of regenerating limbs/fins in urodeles (salamanders and newts), anurans (frogs), and zebrafish, there is strong evidence that Fgf signaling is required for the early stages of regeneration. Using histology, cell labeling, microscopy, and gene expression, the investigator will verify the model of joint regeneration. Using growth factor delivery (gain of function), inhibitor analysis (loss of function), and RT-PCR, she will verify a role for FGFs in the initiation of regeneration. 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 test the model of joint regeneration and the hypothesis that Fgf(s) is required for the initiation of joint regeneration in the developing chick. This work will lay a foundation that will have significant implications in the fields of joint development and regenerative medicine.

描述（由申请人提供）：滑膜关节，如手肘、膝关节和髋关节，对于日常生活中的功能极其重要。 滑膜关节的先天性缺陷、疾病和创伤，特别是构成关节的关节软骨，使数十亿人衰弱。 由于缺乏全关节置换术，使关节恢复正常功能的治疗方法非常缺乏。 阻碍临床措施的进展是关节软骨固有的不能自我修复或再生。 因此，在基于再生的关节修复程序之前，即，再生医学，要测试和利用，必须有一个组成关节的组织的再生过程的理解。 然而，到目前为止，还没有一项研究集中在滑膜关节的再生。 研究者提出了一个关节再生的模型和一个新的手段，研究再生过程。 使用鸡胚模型，她的初步数据表明，假定的肘关节能够在切除后再生，并且这种能力随后随着发育年龄的增加而丧失，这一点可以通过肘关节的缺乏以及元素之间的软骨融合来证明。 所提出的关节再生模型认为，包括手肘、肱骨、桡骨和尺骨的预期骨骼元件的细胞首先被观察到为连续的间充质凝聚。 观察到与软骨形成前或早期凝聚相关的基因。 随后，这些基因在关节形成区域下调，并且调节关节形态发生的基因在再生关节中表达。 研究者的模型声称，在愈合过程中缺乏关节形态发生信号，导致在肢体中形成骨骼元件而没有介入肘关节。 除了这种关节再生模型之外，她还假设，由于成纤维细胞生长因子（FGF）家族成员的存在和/或激活，小鸡肘关节在切除后能够启动再生。 基于对有尾目动物（蝾螈和蝾螈）、无尾目动物（青蛙）和斑马鱼的肢体/鳍再生的研究，有强有力的证据表明，再生的早期阶段需要FGF信号传导。 使用组织学、细胞标记、显微镜和基因表达，研究者将验证关节再生模型。 使用生长因子传递（功能获得），抑制剂分析（功能丧失）和RT-PCR，她将验证FGF在再生启动中的作用。 该项目的长期目标是阐明组成关节的组织再生所需的因素，包括肌肉，骨骼和软骨。 具体目的是测试关节再生的模型和假设，即Fgf（s）是启动发育中的鸡关节再生所必需的。 这项工作将奠定一个基础，将在联合开发和再生医学领域产生重大影响。