Department of Orthopaedics, Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Biomed Res Int. 2019 Jul 4;2019:1283717. doi: 10.1155/2019/1283717. eCollection 2019.
To investigate whether angiogenesis changes in early menopausal osteoporosis treated with estrogen replacement therapy, 120 rats were randomly divided into five groups: sham operation group (SHAM), ovariectomy group (OVX), and ovariectomy plus three different estrogen doses replacement therapy groups (OVX + E2). We detected the bone microarchitecture and measured the expression levels of estrogen receptor beta (ER), vascular endothelial growth factor (VEGF), osteoprotegerin (OPG), and receptor activator of NF-B ligand (RANKL). CD31 immunofluorescence and silica gel perfusion imaging were used to analyze the vascular distribution. We confirmed that the femur BMD of ovariectomized rats was significantly lower than SHAM group and OVX+E2 groups. After estrogen therapy, the local microvascular formation increased after estrogen treatment in a dose dependent manner. ER was downregulated and VEGF was upregulated, positively correlated with estrogen dosage. We successfully constructed an osteoporosis model of ovariectomized rats with estrogen replacement therapy. We also found angiogenesis changed in early menopausal osteoporosis treated with estrogen replacement therapy. We indicated that estrogen replacement therapy increased angiogenesis through VEGF upregulation. However, we observed that, at the highest doses of estrogen studied, increased angiogenesis was associated with a decrease in BMD, the underlying mechanisms of which remain unclear.
为了研究雌激素替代疗法治疗绝经早期骨质疏松症时血管生成的变化，将 120 只大鼠随机分为五组：假手术组（SHAM）、卵巢切除术组（OVX）和卵巢切除术加三种不同雌激素剂量替代治疗组（OVX+E2）。我们检测了骨微结构，并测量了雌激素受体β（ER）、血管内皮生长因子（VEGF）、护骨素（OPG）和核因子-B 配体受体激活剂（RANKL）的表达水平。通过 CD31 免疫荧光和硅胶灌注成像分析血管分布。我们证实，卵巢切除大鼠的股骨 BMD 明显低于 SHAM 组和 OVX+E2 组。雌激素治疗后，雌激素治疗以剂量依赖的方式增加局部微血管形成。ER 下调，VEGF 上调，与雌激素剂量呈正相关。我们成功构建了雌激素替代治疗的去卵巢大鼠骨质疏松模型。我们还发现，雌激素替代治疗可改变绝经早期骨质疏松症的血管生成。我们表明，雌激素替代疗法通过上调 VEGF 增加了血管生成。然而，我们观察到，在所研究的最高雌激素剂量下，增加的血管生成与 BMD 降低有关，其潜在机制尚不清楚。
