ENDOSTEAL BONE VOLUME REGULATION AND OSTEOPOROSIS

这项工作的建议是致力于研究的调控骨内膜骨 音量. 这些研究对我们的总体长期目标至关重要， 治疗和预防骨质疏松症。 我们的观点是在骨质疏松症中， 骨内膜骨体积丢失，即骨内膜骨体积调节缺陷 解释了这种骨质流失，这种缺陷可能涉及我们假定的 耦合因子 钙调节激素对大鼠脑缺血再灌注损伤作用的研究 骨内膜导致了这样的概念， 骨内膜反调节作用是骨吸收增加后， 由偶联因子介导并起维持骨内膜功能的措施 骨体积与钙调节激素相反。 我们将测试我们的 假设，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 然后将纯化因子;其分泌、特异性和 将研究行动。 此外，我们会研究规管 四种骨细胞群（定型和成熟）之间的相互作用 成骨细胞和破骨细胞）响应于仅一个 这些细胞群体。 后者将包括对IA大鼠的研究， 破骨细胞群的活动可能仅仅是 受损，以及用顺式羟脯氨酸治疗的研究， 可以专门抑制成骨细胞群的活性。 为 这些研究中，我们将开发一种氚标记的胸苷动力学方法， 测量成骨细胞和破骨细胞的细胞生产率， 定向成骨细胞和定向破骨细胞群体的测量 分别 该方法也可应用于W/Wv的研究 具有干细胞缺陷的小鼠，其可以提供一种手段， 确定成骨细胞数量与破骨细胞数量的耦合， 我们已经记录的发现，在干细胞水平上起作用。

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.