HORMONAL REGULATION OF BONE GROWTH IN VIVO

这项多因素提案的主要目标是继续研究 甲状旁腺激素，甲状旁腺激素，矛盾的机制 被认为是骨骼的分解代谢激素，可以刺激骨骼生长 活着。我们已经开发了一种可在体内重现的模型，方法是 间歇性合成人甲状旁腺素1-34对幼年大鼠的增骨作用 质量和骨形成表面。 一个具体的目标是确定与增长有关的因素，如 作为生长激素(GH)，生长激素依赖的胰岛素样生长因子(IGF-I) 营养调节甲状旁腺素诱导的幼鼠和幼鼠的合成代谢反应 老化的老鼠。新提出的模型包括去垂体的大鼠，使用 生长抑素类似物抑制生长激素和遗传生长缺陷小鼠。 第二个具体目标是使用一种新的体内-体内方案 甲状旁腺素诱导的合成代谢反应以确定甲状旁腺素是否刺激 分泌局部生长因子，特别是IGF-I和TGFbeta。 免疫细胞化学正在发展以定位IGF-I和 组织学骨切片中的转化生长因子β分泌。第三个具体目标 是研究骨细胞动力学，以确定合成代谢的影响 甲状旁腺激素对成骨细胞分化和成骨细胞前体的影响 复制。介绍的技术包括已建立的和新的 体内和新的体内-体外方法，使用化学，生化， 我开发的计算机辅助形态测量和放射自显影方法 评估骨量和生长的变化，并应用最新的 骨生长因子研究进展。一种新的体内模型 研究甲状旁腺激素和局部骨生长因子的直接作用 建议，使用动脉内注入的大鼠后肢。 对调节合成代谢作用的机制和介体的认识 将提供一个更合理的基础来证明目前使用的 甲状旁腺激素在治疗骨质疏松症中的作用 刺激多种骨质疏松症患者骨生长的治疗方法 骨病。

The main goal of this multifacted proposal is to continue research on the mechanisms by which parathyroid hormone, PTH, paradoxically considered a catabolic hormone for bone, can stimulate bone growth in vivo. We have developed a reproducible in vivo model by giving intermittent synthetic human PTH 1-34 to young rats to increase bone mass and bone forming surfaces. A specific goal is to determine how factors associated with growth, such as growth hormone (GH), GH-dependent insulin-like growth factor (IGF-I) and nutrition regulate the PTH-induced anabolic response in young and aging rats. New models proposed include hypophysectomised rats, the use of somatostatin analog suppress GH and mice with genetic growth defects. A second specific goal is to use a new in vivo-in vivo protocol of the PTH-induced anabolic response to determine if PTH stimulates the secretion of local growth factors, specifically IGF-I and TGFbeta. Immunocytochemistry is being developed to localise sites of IGF-I and TGFbeta secretion in histologic bone sections. The third specific goal is to investigate bone cell kinetics to determine the effect of anabolic doses of PTH on osteoblast differentiation and osteoblast precursor replication. The techniques described include established and new in vivo and new in vivo-in vitro approaches, using chemical, biochemical, computer-assisted morphometric and autoradiographic methods I developed to assess changes in bone mass and growth, and applying recent developments in bone growth factor research. A new in vivo model to study the direct effects of PTH and local bone growth factors is proposed, using intra-arterial infusion of a rat hindlimb. Knowledge of the mechanisms and mediators regulating the anabolic effect of PTH would provide a more rational basis to justify the current use of PTH in the treatment of osteoporosis and might suggest new approaches to therapies to stimulate bone growth in a wide variety of patients with bone diseases.