The role of estrogen in the control of rat osteocyte apoptosis
The role of estrogen in the control of rat osteocyte apoptosis
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DOI：
10.1359/jbmr.1998.13.8.1243
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发表时间：
1998-08-01
影响因子：
6.2
通讯作者：
Noble, BS
中科院分区：
文献类型：
--
作者：
Tomkinson, A;Gevers, EF;Noble, BS
我们之前的研究表明，促性腺激素释放激素类似物（GnRHa）的雌激素戒断可通过人骨细胞凋亡诱导骨细胞死亡。虽然通过细胞凋亡导致的骨细胞死亡的增加可能与雌激素的丧失有关，但这些实验不能排除GnRHa的直接作用。因此，在本研究中，我们使用大鼠卵巢切除（OVX）模型来确定雌激素停药的影响是否延伸到其他物种，并阐明雌激素在维持骨细胞活力中的作用。将12只9周龄大鼠分为假手术组（sham） （n = 4）、OVX （n = 4）、OVX +雌激素（E2） （25 μ g/d） （n = 4） 3组。治疗开始后3周，切除胫骨。使用原位镍翻译方法，OVX组显示DNA断裂的骨细胞百分比在皮质骨（分别为10.04%对2.31%,p < 0.0001）和小梁骨（分别为6.44%对1.58%,p = 0.003）中均显著高于SHAM对照组。在OVX动物中添加雌激素完全消除了皮质骨（0.78%）和小梁骨（1.17%）骨细胞凋亡的增加。在OVX模型和OVX + E2模型中，凋亡的骨细胞百分比随着离生长板下方初级/次级海绵界面距离的增加而降低。细胞核形态学和DNA电泳证实了样品中凋亡细胞的存在。综上所述，大鼠的OVX直接或间接导致E2丢失导致骨细胞凋亡增加。在OVX动物中添加雌激素可防止骨细胞凋亡的增加。这些数据证实了雌激素在控制骨细胞凋亡和维持骨细胞活力方面的重要作用。雌激素缺乏可能通过损害骨细胞网络的活力，降低骨对负荷的适当反应能力。
We have previously shown that estrogen withdrawal by gonadotrophin-releasing hormone analogs (GnRHa) induces osteocyte death via apoptosis in human bone. Although it is likely that the increase in osteocyte death via apoptosis was related to the loss of estrogen, these experiments could not rule out a direct role for the GnRHa. Therefore, in this study, we have used a rat model of ovariectomy (OVX) to determine whether the effect of estrogen withdrawal extends to other species and to clarify the role of estrogen in the maintenance of osteocyte viability. Twelve 9-week-old rats were divided into three treatment groups: sham operated (SHAM) (n = 4), OVX (n = 4), and OVX + estrogen (E2) (25 mu g/day) (n = 4). At 3 weeks following the start of treatment, tibial bones were removed. The percentage of osteocytes displaying DNA breaks, using an in situ nick-translation method, was significantly higher in the OVX group compared with the SHAM control in both cortical bone (10.04% vs. 2.31%, respectively; p < 0.0001) and trabecular bone (6.44% vs. 1.58%, respectively; p = 0.003). Addition of estrogen in the OVX animals completely abrogated the increase in osteocyte apoptosis in cortical bone (0.78%) and trabecular bone (1.17%). The percentage of apoptotic osteocytes decreased with increasing distance from the primary/secondary spongiosa interface below the growth plate in the OVX model and the OVX + E2 model. Nuclear morphology and electrophoresis of DNA confirmed the presence of apoptotic cells in the samples. In conclusion, OVX in the rat results in an increase in osteocyte apoptosis as a direct or indirect result of E2 loss. Addition of estrogen in the OVX animals prevents this increase in osteocyte apoptosis. These data confirm an important role for estrogen in the control of osteocyte apoptosis and the maintenance of osteocyte viability. Estrogen deficiency might, through compromising the viability of osteocyte networks, reduce the ability of bone to respond appropriately to loading.