Adenosine A(1) receptors regulate bone resorption in mice: adenosine A(1) receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A(1) receptor-knockout mice.
Adenosine A(1) receptors regulate bone resorption in mice: adenosine A(1) receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A(1) receptor-knockout mice.
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DOI：
10.1002/art.27219
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发表时间：
2010-02
影响因子：
--
通讯作者：
Cronstein, Bruce N.
中科院分区：
文献类型：
--
作者：
Kara, Firas M.;Doty, Stephen B.;Boskey, Adele;Goldring, Steven;Zaidi, Mone;Fredholm, Bertil B.;Cronstein, Bruce N.
加速的破骨细胞性骨吸收在骨质疏松症和其他骨病的发病机制中起着核心作用。由于识别调节破骨细胞活性的分子途径为了解这些疾病的原因和开发新的治疗方法提供了关键，我们研究了腺苷A1受体阻断或缺失对骨密度的影响。用DEXA扫描分析腺苷A1受体基因敲除小鼠的骨密度(BMD)，用Micro CT测定骨小梁体积和皮质骨体积。小鼠去卵巢或假手术，术后5周出现骨量减少时，用DEXA扫描和MicroCT分析几个参数。对A1基因敲除小鼠和野生型小鼠的骨骼进行了组织学检查。用荧光显微镜观察四环素双标记后的成骨细胞功能(骨形成)。对A1KO小鼠骨骼的MicroCT分析显示，骨体积显著增加。A1KO小鼠骨骼的电子显微镜显示，没有破骨细胞的褶皱边缘和破骨细胞骨吸收。免疫组织学显示，虽然破骨细胞存在于A1KO小鼠中，但它们较小，而且通常与骨骼无关。没有观察到成骨细胞的形态变化，骨标记研究显示A1KO小鼠的骨形成率没有变化。这些结果表明，腺苷A1受体可能是治疗骨质疏松和假体关节松动等以过度骨转换为特征的疾病的有用靶点。
Accelerated osteoclastic bone resorption plays a central role in the pathogenesis of osteoporosis and other bone diseases. Because identifying the molecular pathways that regulate osteoclast activity provides a key to understanding the causes of these diseases and to the development of new treatments we studied the effect of adenosine A1 receptor blockade or deletion on bone density. Bone mineral density (BMD) in adenosine A1 receptor knockout mice was analyzed by DEXA scan and the trabecular and cortical bone volume was determined by Micro CT. Mice were ovariectomized or sham-operated, and 5 weeks after surgery, when osteopenia had developed, several parameters were analysed by DEXA scan and MicroCT. Histological examination of bones from A1 knockout and wild type mice was carried out. Visualization of osteoblast function (bone formation) after Tetracycline double labeling was performed by fluorescence microscopy. MicroCT analysis of bones from A1KO mice showed significantly increased bone volume. Electron microscopy of bones from A1KO mice shows an absence of ruffled borders of osteoclasts and osteoclast bone resorption. Immunohistology demonstrates that although osteoclasts are present in the A1KO mice they are smaller and often not associated with bone. No morphologic changes in osteoblasts were observed and bone labeling studies reveal no change in bone formation rates in the A1KO mice. These results suggest that the adenosine A1 receptor may be a useful target in treating diseases characterized by excessive bone turnover such as osteoporosis and prosthetic joint loosening.
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DOI：
10.1073/pnas.0508480102
发表时间：
2005-11-22
影响因子：
11.1
作者：
Sun, L;Blair, HC;Zaidi, M
通讯作者：
Zaidi, M
影响因子：
7.3
作者：
Chan, Edwin S. L.;Montesinos, Maria Carmen;Cronstein, Bruce N.
通讯作者：
Cronstein, Bruce N.
影响因子：
15.9
作者：
Bianco, P;Robey, PG
通讯作者：
Robey, PG
DOI：
10.1073/pnas.161292398
发表时间：
2001-07-31
影响因子：
11.1
作者：
Johansson, B;Halldner, L;Fredholm, BB
通讯作者：
Fredholm, BB
影响因子：
4.9
作者：
Schett G
通讯作者：
Schett G