ENDOSTEAL BONE VOLUME REGULATION AND OSTEOPOROSIS

这项拟议的工作致力于研究骨内膜骨的调节。 音量。这类研究对我们的整体长远目标至为重要。 治疗和预防骨质疏松症。我们的立场是，在骨质疏松症方面， 骨内膜骨体积丢失，即有缺陷的骨内膜骨体积调节 造成了这种骨丢失，而且这种缺陷可能与我们推测的 耦合系数。钙调节激素对心脏功能影响的研究 骨内膜导致了一种概念，即在形成过程中耦合的增加 在骨吸收增加之后是骨内膜的反调节 由偶联因子介导的维持骨内膜功能的测量 骨量与钙调节激素相反。我们将测试我们的 假说，通过体外研究，在骨吸收过程中 偶联因子从骨基质或骨内膜释放 细胞。然后将纯化该因子(S)；它的分泌、特异性和 将对行动进行研究。此外，我们还将研究监管 四种骨细胞群(成熟型和成熟型)之间的相互作用 成骨细胞和破骨细胞)响应于仅以下之一的扰动 这些细胞群。后者将包括对IA大鼠的研究 破骨细胞群体的活动可能是唯一的 损伤，以及用顺式羟脯氨酸治疗的研究，顺式羟脯氨酸 可以专一地抑制成骨细胞群体的活性。为 这些研究我们将开发一种氚胸苷动力学方法来 测量成骨细胞和破骨细胞的细胞生成率 已承诺的成骨细胞和已承诺的破骨细胞数量的测量 分别进行了分析。该方法也将应用于W/W V的研究 具有干细胞缺陷的小鼠，它可能提供一种手段 确定成骨细胞数量与破骨细胞数量的耦合，a 我们已经记录的发现，是在干细胞水平上运作的。

The proposed work is devoted to studies of the regulation of endosteal bone volume. Such studies are essential to our overall long-term goal, which is to cure and prevent osteoporosis. Our position is that in osteoporosis, endosteal bone volume is lost, that faulty endosteal bone volume regulation accounts for this bone loss, and that this defect may involve our putative coupling factor. Studies of the effects of calcium regulating hormones at the endosteum led to the concept that the coupled increase in formation subsequent to an increase in resorption was an endosteal counter-regulatory measure mediated by a coupling factor and functioning to maintain endosteal bone volume in opposition to calcium regulating hormones. We will test our hypothesis, by means of in vitro studies, that during bone resorption a coupling factor is liberated either from bone matrix or from endosteal bone cells. The factor(s) will then be purified; its secretion, specificity and action will be studied. In addition, we will study the regulatory interactions among the four bone cell populations (committed and mature osteoblasts and osteoclasts) in response to a perturbation of only one of these cell populations. The latter will include studies of the ia rat in which the activity of the osteoclast population is probably exclusively impaired, and studies of treatment with cis-hydroxyproline, an agent that may exclusively inhibit the activity of the osteoblast population. For these studies we will develop a tritiated thymidine kinetic method to measure cell production rates of osteoblasts and osteoclasts which will be measures of the committed osteoblast and committed osteoclast populations respectively. This method also will be applied to the studies of the W/Wv mouse which has a stem cell defect and which may provide a means to determine if the coupling of osteoblast number to osteoclast number, a finding which we have documented, operates at the stem cell level.