内分泌学
血管紧张素II
内科学
兰克尔
下调和上调
受体
骨吸收
血管紧张素Ⅱ受体1型
化学
骨重建
氯沙坦
骨质疏松症
骨矿物
成骨细胞
医学
体外
生物化学
基因
激活剂(遗传学)
作者
Yi Zhou,Xiaoxu Guan,Xiaoyi Chen,Mengfei Yu,Chaowei Wang,Xuepeng Chen,Jiejun Shi,Tie Liu,Huiming Wang
出处
期刊:Cells Tissues Organs
[S. Karger AG]
日期:2017-01-01
卷期号:204 (1): 25-37
被引量:17
摘要
Animal studies have reported on the benefits of ARB on bone mass. However, the underlying mechanism for angiotensin II (AngII)/AngII receptor blockade (ARB) in regulating bone mass remains elusive. Since high levels of plasma and urine cAMP are observed in osteoporotic and hypertensive patients, we hypothesized that cAMP may be an important molecule for the downstream events of the activation of AT receptors, members of the G-protein-coupled receptor family, in regulating bone turnover. In this study, micro-CT and X-ray analyses indicated that AngII decreased bone mass via biasing bone resorption over bone formation in osteoporotic mice. However, these adverse effects were blocked by olmesartan and PD123319. In vitro, AngII was shown to downregulate osteogenic differentiation and matrix mineralization, but to upregulate osteoclastic activity by mainly affecting osteoblasts producing osteoclastogenesis-associated key soluble factors, including M-CSF and RANKL. Similarly, ARB treatment exhibited antagonistic effects on AngII. In conclusion, osteoblasts are the directly targeted cells. ARB1 exhibits a greater capacity to increase bone mass than ARB2. The cAMP-dependent PKA pathway plays an important role in AngII/ARB on changing bone mass.
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