INTERLEUKIN 6 AND OSTEOPOROSIS

白细胞介素 6 与骨质疏松症

• 批准号: 2053292
• 负责人: William B. Ershler
• 金额: $ 33.56万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-15 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2053292
• 关键词: Macaca mulatta; biological models; bone density; bone metabolism; estrogens; female; gene expression; histology; hormone regulation /control mechanism; interleukin 6; osteoporosis; ovariectomy; postmenopause; radiography

DESCRIPTION: (Adapted from the Investigator's abstract) This is a revised application for a proposed research project that has, as its central goal, determining the importance of interleukin-6 (IL-6) dysregulation in the pathogenesis of post menopausal osteoporosis. Substantial changes include a better description of the methods of quantifying IL-6 expression and more substantial preliminary results. The project has been modified in other ways in response to prior review and the applicants believe that this is a significantly stronger proposal. The laboratory has focused on various aspects of age- associated immune dysfunction for the past decade. They have found that one molecule, Interleukin-6 (IL-6), is particularly interesting because its expression increases with age. They feel it may contribute to certain age-related maladies including osteoporosis. It is their hypothesis that estrogen inhibits IL-6 gene expression in bone and that one reason for the rise in IL-6 levels in postmenopausal women is the loss of the inhibitory influence of estrogen. Recently it has been shown that IL-6 enhances osteoclast formation in rodents. Therefore, one mechanism whereby estrogen deficiency might result in bone resorption is by the associated rise in IL-6 and increased osteoclast activity. In the current research the investigators intend to explore this hypothesis in rhesus monkeys. Twenty middle-aged (10-15 years) female monkeys will be subjected to oophorectomy and ten of these will have estrogen replacement. Five additional age-matched controls will be followed without oophorectomy (sham-operated controls). Blood, urine and bone specimens will be obtained and dual energy x-ray absorptiometry (DXA) will be used to assess bone mineral density. Furthermore, the level of IL-6 gene expression by osteoblasts and other bone cells in the various bone envelopes will be analyzed in the context of estrogen status. IL-6 expression will also be correlated with bone mineral content (DXA), bone strength and histomorphometry. If their hypotheses are true, they will have shown in a primate model that IL-6 expression in cancellous and endocortical bone envelopes (but perhaps not in Haversian envelopes) is regulated by estrogen and that when estrogen levels are low, increased bone turnover and decreased bone strength is the result. This research will also be of value because it will provide useful longitudinal data on bone density, histomorphometry and bone strength in this important animal model.

描述：（改编自研究者摘要）这是一份 修订申请的拟议研究项目，作为其 中心目标，确定白细胞介素-6（IL-6）的重要性 绝经后骨质疏松症的发病机制中的失调。 实质性的变化包括更好地描述方法， 定量IL-6表达和更实质性的初步结果。 该项目已在其他方面进行了修改，以回应事先审查 申请人认为这是一个明显更强的 提议 该实验室专注于年龄的各个方面- 相关的免疫功能紊乱 他们发现 其中一种分子，白细胞介素-6（IL-6），特别令人感兴趣， 其表达随年龄增长而增加。 他们认为这可能有助于 某些与年龄有关的疾病，包括骨质疏松症。 这是他们 假设雌激素抑制骨中IL-6基因表达， 绝经后妇女IL-6水平升高的一个原因是 雌激素抑制作用的丧失。 最近已经 显示IL-6增强啮齿动物中破骨细胞的形成。 因此，一 雌激素缺乏可能导致骨吸收的机制 是通过IL-6的相关升高和破骨细胞活性的增加。 在目前的研究中，研究人员打算探索这一点。 假设在恒河猴中。 20名中年（10-15岁）女性 猴子将接受卵巢切除术，其中10只将 雌激素替代品 另外5个年龄匹配的对照组将 随后不进行卵巢切除术（假手术对照）。 血液、尿液 并将获得骨标本， (DXA)将用于评估骨密度。 而且 成骨细胞和其他骨细胞的IL-6基因表达水平 将在雌激素的背景下分析各种骨包膜 status. IL-6的表达也与骨矿物质相关 含量（DXA）、骨强度和组织形态计量学。 如果他们的假设 如果是真的，他们将在灵长类动物模型中显示IL-6表达 在松质骨和皮质骨包膜中（但可能不在 哈弗氏囊膜）受雌激素调节，当雌激素 水平低，增加骨转换和降低骨强度， 结果。 这项研究也将是有价值的，因为它将提供 关于骨密度、组织形态计量学和骨的有用纵向数据 在这个重要的动物模型中。