ESTROGEN ACTION ON OSTEOCLASTS IN VITRO

在成年生活中，正常的骨代谢包括以下平衡： 破骨细胞介导的再吸收和成骨细胞介导的形成。 这 平衡，称为耦合，保持整个骨量 成人早期生活 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、佩吉特、骨关节炎）， 遗传性（骨生成异常，骨硬化），传染性 （牙周病）和肿瘤（骨肉瘤，巨细胞瘤）， 涉及骨的吸收-形成偶联异常 重塑 骨吸收率是由数量和 破骨细胞的活性。 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， 或间接地。 在临床上，破骨细胞功能障碍是一个主要因素， 绝经后骨质疏松症 荷尔蒙的显著变化， 开始与更年期的发病最有可能牵连 骨质疏松 首席研究员最近发现， 雌激素受体mRNA和功能性受体的存在， 鸟类破骨细胞，并证明直接调节骨细胞骨 再吸收 拟议研究的目的是扩大 以前报道过雌激素对鸟类的直接影响 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，介导 这个回应。 这些拟议研究的具体目标是：1） 鸟类破骨细胞和人类巨细胞雌激素受体鉴定 肿瘤，2）定量和表征雌激素对禽类的影响， 大鼠和人破骨细胞再吸收活性，3）评估 雌激素对所选破骨细胞蛋白基因表达的影响， 参与再吸收过程，4）评估 雌激素对所选破骨细胞蛋白水平和/或活性的影响。 分离 禽类破骨细胞、人破骨细胞和破骨细胞瘤以及大鼠 将用雌激素刺激破骨细胞，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）将在禽类中进行检查。 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.