PEPTIDE GROWTH FACTORS AND SKELETAL DEVELOPMENT

描述：(改编自《调查者摘要》)几乎全部 骨骼的生长是骨骼有序分裂和成熟的结果 骨骺生长板的细胞。正常骨骼发育 取决于对这一过程的适当控制。这项建议是 根据申请者之前的观察，多肽增长 这些因素参与了这一控制。拟议研究的目标是 就是阐明选定的生长因子调节的机制 生长板软骨细胞。研究人员假设， 要素相互作用在生长调控中发挥着重要作用 板状软骨细胞。这些研究的目的之一就是检验这一假设。 通过考察选定生长的个体和交互效应 影响有丝分裂和分化软骨细胞功能的因素 在试管中。细胞培养，代谢标记，放射免疫分析， 将使用免疫抑制、Northern和原位杂交方法 以确定相互作用并开始阐明其机制。这个 第二个目的是检验这样一种假设，即促钙作用 生长板软骨细胞上的激素降钙素和甲状旁腺素受到调节 由多肽生长因子组成。具体地说，软骨细胞甲状旁腺素的调节 部分生长因子对受体和降钙素受体表达的影响 将通过细胞生物学和分子生物学技术进行检测。 第三个目标是评估外源性给药的能力 调节活体骨骼生长的生长因子。使用大鼠模型， 选定因素的作用和相互作用将通过以下方式进行评估 代谢和原位杂交技术。长期目标 这些研究的目的是帮助人们对 调节骨骼生长的机制。只有拥有这样的信息，才能 了解骨骼生长和修复的异常，以及 生长因子最终对临床问题的潜在贡献 要下定决心。

DESCRIPTION: (Adapted From Investigator's Abstract) Virtually all skeletal growth is the result of the orderly division and maturation of the cells of the epiphyseal growth plate. Normal skeletal development is dependent on the proper control of this process. This proposal is based on the applicants' previous observations that peptide growth factors participate in this control. The goal of the proposed studies is to elucidate the mechanisms by which selected growth factors regulate growth plate chondrocytes. The investigators hypothesize that growth factor interaction plays an important role in the regulation of growth plate chondrocytes. One aim of these studies is to test this hypothesis by examining the individual and interactive effects of selected growth factors with respect to mitotic and differentiated chondrocyte functions in vitro. Cell culture, metabolic labelling, radioimmunoassay, immunoinhibition, Northern and in situ hybridization methods will be used to identify interactions and begin to elucidate their mechanisms. The second aim is to test the postulate that the effects of the calciotropic hormones, calcitonin and PTH, on growth plate chondrocytes are modulated by peptide growth factors. Specifically, regulation of chondrocyte PTH receptor and calcitonin receptor expression by selected growth factors will be examined by cell biological and molecular biological techniques. The third aim is to assess the ability of exogenously administered growth factors to regulate skeletal growth in vivo.Using a rat model, the action and interaction of selected factors will be evaluated by metabolic and in situ hybridization techniques. The long-term objective of these studies is to help achieve a basic understanding of the mechanisms regulating skeletal growth. Only with such information can abnormalities of skeletal growth and repair be understood and the potential contribution of growth factors to clinical problems eventually be determined.