GLUCOCORTICOID ACTIONS ON OSTEOCLASTS

牙周病期间发生的慢性炎症反应 通常由于牙槽骨的破坏而导致牙齿脱落。 这种破坏在一定程度上可能是破骨细胞的结果。 慢性炎症细胞产生的细胞因子的刺激。在……里面 成人生活中，正常的骨骼代谢涉及破骨细胞- 介导的吸收和成骨细胞介导的形成。这种平衡， 称为耦合，不会导致整体骨骼的净变化 在整个成年生活中。大多数与骨骼系统有关的疾病 如感染性(牙周病)、代谢性(骨关节炎、 骨质疏松症，肾性骨营养不良，Paget‘s)，遗传性(成骨 不完全性骨化症)和基于肿瘤的(骨肉瘤、巨细胞 肿瘤)，涉及吸收-形成耦合的异常。骨 吸收率由数量和活动水平共同决定。 破骨细胞。许多激素信号可能影响破骨细胞 招聘、差异化和/或活动，直接或 间接的。类风湿的临床糖皮质激素治疗 关节炎改善了牙周组织的健康，但矛盾的是， 治疗通常会导致糖皮质激素引起的骨质疏松。这个 糖皮质激素影响骨代谢的机制尚不清楚 明白了。有许多关于成骨细胞对 糖皮质激素治疗，但糖皮质激素对 骨吸收则显示出相反的结果。在这份文件中提供的证据 应用表明，高纯度的破骨细胞含有 糖皮质激素受体与糖皮质激素对破骨细胞的调节 骨吸收。拟议研究的目标是验证 糖皮质激素对破骨细胞骨吸收的直接影响 以确定这种反应的一些细胞效应器。这个 这些研究的具体目的是：1)识别和量化 禽类破骨细胞和人巨细胞瘤中的糖皮质激素受体 (破骨细胞瘤)，2)量化和表征 糖皮质激素对破骨细胞吸收活性的影响，3)分析 糖皮质激素对破骨细胞核原癌基因的影响 4)评价糖皮质激素对破骨细胞的影响 核原癌基因的表达，以及，4)评估 糖皮质激素对破骨细胞蛋白基因表达的影响 与吸收过程有牵连。隔离禽类 破骨细胞和人类破骨细胞瘤将被用来表征 破骨细胞糖皮质激素受体。此外，禽类破骨细胞和 人破骨细胞瘤培养物将受到糖皮质激素的挑战 糖皮质激素对骨吸收的影响及基因研究 体外反应。

The chronic inflammatory response which occurs during periodontal disease often results in tooth loss due to the destruction of alveolar bone. This destruction is likely, in part, to be the result of osteoclast stimulation by cytokines produced by the chronic inflammatory cells. In adult life, normal bone metabolism involves a balance between osteoclast- mediated resorption and osteoblast-mediated formation. this balance, referred to as coupling, results in no net change in overall bone throughout adult life. Most diseases relating to the skeletal system such as infectious (periodontal disease), metabolic (osteoarthritis, osteoporosis, renal osteodystrophy, Paget's), inherited (osteogenesis imperfecta, osteopetrosis), and tumor-based (osteosarcoma, giant cell tumor), involve abnormalities in the resorption-formation coupling. Bone resorption rates are determined by both the number and activity level of osteoclasts. A number of hormonal signals may influence osteoclast recruitment, differentiation, and/or activity either directly or indirectly. Clinically, glucocorticoid treatment for rheumatoid arthritis improves the health of periodontal tissue, but, paradoxically, treatment often results in glucocorticoid-induced osteoporosis. The mechanism by which glucocorticoids influence bone metabolism are not well understood. There are numerous reports of osteoblast responses to glucocorticoid treatments, but studies on glucocorticoid influences on bone resorption have shown opposing results. Evidence presented in this application suggests that highly purified osteoclasts contain glucocorticoid receptors and that glucocorticoids regulate osteoclast bone resorption. The objectives of the proposed studies are to verify the direct influence of glucocorticoids on osteoclast bone resorption and to identify some of the cellular effectors of this response. The specific aims of these studies are to: 1) identify and quantitate glucocorticoid receptors in avian osteoclasts and human giant cell tumors (osteoclastomas), 2) quantitate and characterize the effect of glucocorticoids on osteoclast resorption activity, 3) analyze the influence of glucocorticoids on osteoclast nuclear proto-oncogene expression and, 4) assess the influence of glucocorticoids on osteoclast nuclear proto-oncogene expression and, 4) assess the influence of glucocorticoids on gene expression of selected osteoclast proteins which have been implicated in the resorption process. Isolated avian osteoclasts and human osteoclastomas will be used to characterize osteoclast glucocorticoid receptors. In addition, avian osteoclast and human osteoclastoma cultures will be challenged with glucocorticoids to study the influence of glucocorticoids on bone resorption and gene responses in vitro.