HORMONAL REGULATION OF BONE GROWTH IN VIVO

这项多方面建议的主要目标是继续研究 甲状旁腺激素的机制， 被认为是骨骼的分解代谢激素，可以刺激骨骼生长， vivo. 我们已经开发了一种可重复的体内模型， 间歇性合成人PTH 1-34给幼鼠以增加骨 质量和骨形成表面。 一个具体的目标是确定与增长相关的因素，如 生长激素（GH），GH依赖性胰岛素样生长因子（IGF-I） 和营养调节PTH诱导的合成代谢反应， 衰老的老鼠 提出的新模型包括切除垂体的大鼠， 生长抑素类似物抑制生长激素和遗传性生长缺陷小鼠。 第二个具体目标是使用新的体内-体内方案， 甲状旁腺激素诱导的合成代谢反应，以确定甲状旁腺激素是否刺激 局部生长因子的分泌，特别是IGF-I和TGF β。 正在开发免疫细胞化学来定位IGF-I的位点， 组织学骨切片中的TGF 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， PTH剂量对成骨细胞分化和成骨细胞前体的影响 复制的 所描述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，生物化学， 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，并应用最近的 骨生长因子研究进展。 新的体内模型， 研究PTH和局部骨生长因子的直接作用， 提出，使用大鼠后肢的动脉内输注。 了解调节合成代谢作用的机制和介质 甲状旁腺素的水平将提供一个更合理的基础，以证明目前使用的 PTH在骨质疏松症治疗中的作用，并可能提出新的方法， 刺激各种患者骨生长的疗法， 骨疾病

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.