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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Osteocytes use estrogen receptor alpha to respond to strain but their ERalpha content is regulated by estrogen.
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Osteocytes use estrogen receptor alpha to respond to strain but their ERalpha content is regulated by estrogen.

机译:骨细胞利用雌激素受体α来响应应变,但是它们的ERα含量受雌激素调节。

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The role of mechanical strain and estrogen status in regulating ERalpha levels in bone cells was studied in female rats. OVX is associated with decreased ERalpha protein expression/osteocyte, whereas habitual strain and artificial loading has only a small but positive effect, except on the ulna's medial surface, where artificial loading stimulates reversal of resorption to formation. INTRODUCTION: Osteoporosis is the most widespread failure of bones' ability to match their architectural strength to their habitual load bearing. In men and women, the severity of bone loss is associated with bioavailability of estrogen. This association could result from the estrogen receptor (ER) involvement in bone cells' adaptive response to loading. MATERIALS AND METHODS: In vivo semiquantitative analysis of the amount of ERalpha protein per osteocyte was performed in immuno-cytochemically stained sections from control and loaded rat ulna, as well as tibias of ovariectomy (OVX) and sham-operated female rats. In vitro,the effect of exogenous estrogen (10(-8) M) and mechanical strain (3400 microepsilon, 1 Hz, 600 cycles) on the expression of ERalpha mRNA levels was assessed in ROS 17/2.8 cells in monolayers using real-time PCR and ER promoter activity. ERalpha translocation in response to exogenous estrogen and mechanical strain was assessed in both ROS 17/2.8 and MLO-Y4 cells. RESULTS: More than 90 percent of tibial osteocytes express ERalpha, the level/osteocyte being higher in cortical than cancellous bone. OVX is associated with decreased ERalpha protein expression/osteocyte, whereas in the ulna habitual strain and that caused by artificial loading had only a small but positive effect, except on the medial surface, where loading stimulates reversal of resorption to formation. In unstimulated osteocytes and osteoblasts in situ, and osteocyte-like and osteoblast-like cells in vitro, ERalpha is predominantly cytoplasmic. In vitro, both strain and estrogen stimulate transient ERalpha translocation to the nucleus and transient changes in ERalpha mRNA. Strain but not estrogen also induces discrete membrane localization of ERalpha. CONCLUSIONS: Bone cells' responses to both strain and estrogen involve ERalpha, but only estrogen regulates its cellular concentration. This is consistent with the hypothesis that bone loss associated with estrogen deficiency is a consequence of reduction in ERalpha number/activity associated with lower estrogen concentration reducing the effectiveness of bone cells' anabolic response to strain.
机译:在雌性大鼠中研究了机械应变和雌激素状态在调节骨细胞中ERalpha水平中的作用。 OVX与ERalpha蛋白表达/骨细胞减少有关,而习惯性应变和人工负荷仅对尺骨内侧表面有很小但积极的影响,因为在尺骨内侧表面,人工负荷刺激了吸收的逆转形成。简介:骨质疏松症是骨骼将建筑强度与习惯性承重相匹配的能力中最普遍的失败。在男性和女性中,骨质流失的严重程度与雌激素的生物利用度有关。这种联系可能是由于雌激素受体(ER)参与骨细胞对负荷的适应性反应。材料与方法:在体内免疫组化染色的正常和负荷大鼠尺骨以及卵巢切除术(OVX)和假手术雌性大鼠胫骨的免疫细胞化学染色切片中,对每个骨细胞中ERalpha蛋白的量进行了体内半定量分析。在体外,通过实时评估ROS 17 / 2.8细胞单层中外源雌激素(10(-8)M)和机械应变(3400 microepsilon,1 Hz,600个周期)对ERalpha mRNA表达的影响PCR和ER启动子活性。在ROS 17 / 2.8和MLO-Y4细胞中都评估了响应外源雌激素和机械应变的ERalpha易位。结果:超过90%的胫骨骨细胞表达ERalpha,皮质中的骨/骨细胞水平高于松质骨。 OVX与ERalpha蛋白表达/骨细胞减少有关,而在尺骨习惯性应变中,由人工加载引起的应变只有很小但积极的影响,除了在内侧表面,加载刺激了吸收的逆转形成。在体外未刺激的骨细胞和成骨细胞,以及体外的骨细胞样和成骨细胞样细胞中,ERalpha主要是细胞质。在体外,菌株和雌激素均刺激瞬时ERalpha转运至细胞核和ERalpha mRNA的瞬时变化。应变而不是雌激素也诱导ERα的离散膜定位。结论:骨细胞对品系和雌激素的反应均涉及ERα,但仅雌激素调节其细胞浓度。这与以下假设相吻合:与雌激素缺乏有关的骨质流失是降低雌激素浓度的ERalpha数量/活性降低的结果,从而降低了骨细胞对菌株的合成代谢反应的有效性。

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