Zaman Gul, Jessop Helen L, Muzylak Mariusz, De Souza Roberto L, Pitsillides Andrew A, Price Joanna S, Lanyon Lance L
Department of Basic Sciences, The Royal Veterinary College, University of London, London, United Kingdom.
J Bone Miner Res. 2006 Aug;21(8):1297-306. doi: 10.1359/jbmr.060504.
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.
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.
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.
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.
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.
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雌激素受体α（ERα）水平方面的作用。卵巢切除（OVX）与骨细胞中ERα蛋白表达降低相关，而习惯性应变和人工加载仅有微小但积极的影响，尺骨内侧表面除外，在该表面人工加载刺激了吸收向形成的逆转。
骨质疏松症是骨骼使其结构强度与其习惯性承重相匹配的能力最普遍的失效情况。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相关。这种关联可能是由于雌激素受体（ER）参与了骨细胞对负荷的适应性反应。
对来自对照和加载的大鼠尺骨以及卵巢切除（OVX）和假手术雌性大鼠胫骨的免疫细胞化学染色切片中每个骨细胞的ERα蛋白量进行体内半定量分析。在体外，使用实时PCR和ER启动子活性评估外源性雌激素（10⁻⁸ M）和机械应变（3400微应变，1 Hz，600个周期）对单层ROS 17/2.8细胞中ERα mRNA水平表达的影响。在ROS 17/2.8和MLO - Y4细胞中评估对外源性雌激素和机械应变的ERα易位情况。
超过90%的胫骨骨细胞表达ERα，皮质骨中每个骨细胞的水平高于松质骨。OVX与骨细胞中ERα蛋白表达降低相关，而在尺骨中，习惯性应变和人工加载引起的应变仅有微小但积极的影响，尺骨内侧表面除外，在该表面加载刺激了吸收向形成的逆转。在未受刺激的原位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，ERα主要位于细胞质中。在体外，应变和雌激素均刺激ERα短暂易位至细胞核以及ERα mRNA的短暂变化。应变而非雌激素还诱导ERα离散地定位于细胞膜。
骨细胞对应变和雌激素的反应均涉及ERα，但只有雌激素调节其细胞浓度。这与以下假设一致，即与雌激素缺乏相关的骨质流失是与较低雌激素浓度相关的ERα数量/活性降低的结果，从而降低了骨细胞对应变的合成代谢反应的有效性。
