ESTROGEN ACTION ON OSTEOCLASTS IN VITRO

在成人生活中，正常的骨骼代谢涉及到以下方面的平衡 破骨细胞介导的吸收和成骨细胞介导的形成。这 平衡，称为耦合，在整个过程中保持整体骨量 成年初期的生活。大多数与骨骼系统有关的疾病，如 代谢(骨质疏松症、肾性骨营养不良、Paget‘s、骨关节炎)、 遗传性(成骨不全、骨化症)，传染性 (牙周病)和肿瘤(骨肉瘤、骨巨细胞瘤)， 涉及骨吸收-形成耦合的异常 改建。骨吸收率由数量和数量决定 破骨细胞活性。一些荷尔蒙信号可能会影响 破骨细胞的募集、分化和/或活性 或者是间接的。临床上，破骨细胞功能障碍是 绝经后骨质疏松症。显著的荷尔蒙变化 绝经期的开始很可能与 骨质疏松。首席调查员最近确认了 雌激素受体mRNA和功能性受体在体外培养中的存在 禽类破骨细胞及其对破骨细胞骨的直接调控 再吸收。拟议研究的目的是扩大 先前报道的雌激素对禽类的直接影响 破骨细胞介导的骨吸收包括哺乳动物雌激素 反应并确定一些细胞效应器 这样的回应。这些拟议研究的具体目的是：1) 家禽破骨细胞和人巨细胞雌激素受体的鉴定 肿瘤，2)量化和表征雌激素对禽类的影响， 大鼠和人破骨细胞的吸收活性，3)评估 雌激素对某些破骨细胞蛋白基因表达的影响 与吸收过程有关，4)评估 雌激素对选定的破骨细胞蛋白水平和/或活性的影响。孤立 禽破骨细胞、人破骨细胞和破骨细胞瘤，以及大鼠 破骨细胞将受到雌激素的挑战，以研究 类固醇激素对骨吸收的影响。基因表达影响(mRNA， 蛋白质水平和酶活性)将在禽类中进行检测 体外培养破骨细胞和人破骨细胞瘤。

In adult life, normal bone metabolism involves a balance between osteoclast-mediated resorption and osteoblast-mediated formation. This balance, referred to as coupling, maintains overall bone mass throughout early adult life. Most diseases relating to the skeletal system, such as metabolic (osteoporosis, renal osteodystrophy, Paget's, osteoarthritis), inherited (osteogenesis imperfecta, osteopetrosis), infectious (periodontal disease) and tumor-based (osteosarcoma, giant cell tumor), involve abnormalities in the resorption-formation coupling of bone remodeling. Bone resorption rates are determined by both the number and activity of osteoclasts. A number of hormonal signals may influence osteoclast recruitment, differentiation, and/or activity either directly or indirectly. Clinically, osteoclast dysfunction is a major factor in postmenopausal osteoporosis. The significant hormonal changes which begin with the onset of menopause are most likely implicated in osteoporosis. The principal investigator has recently identified the presence of estrogen receptor mRNA and functional receptors in isolated avian osteoclasts and demonstrated direct regulation of osteoclastic bone resorption. The objective of the proposed studies is to expand the previously reported direct influence of estrogen on avian osteoclast-mediated bone resorption to include mammalian estrogen responses and to identify some of the cellular effectors which mediate this response. The specific aims of these proposed studies are to: 1) identify estrogen receptors in avian osteoclasts and human giant cell tumors, 2) quantitate and characterize the effects of estrogen on avian, rat and human osteoclast resorptive activity, 3) assess the effects of estrogen on gene expression of selected osteoclast proteins which have been implicated in the resorption process, 4) assess the influence of estrogen on selected osteoclast protein levels and/or activity. Isolated avian osteoclasts, human osteoclasts and osteoclastomas, and rat osteoclasts will be challenged with estrogen to study the influence of steroid hormones on bone resorption. Gene expression influences (mRNA, protein levels, and enzyme activity) will be examined in avian osteoclasts and human osteoclastomas in vitro.