• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Caveolin-1 knockout mice have increased bone size and stiffness.
【24h】

Caveolin-1 knockout mice have increased bone size and stiffness.

机译：Caveolin-1基因敲除小鼠具有增加的骨大小和刚度。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The skeletal phenotype of the cav-1(-/-) mouse, which lacks caveolae, was examined. muCT and histology showed increased trabecular and cortical bone caused by the gene deletion. Structural changes were accompanied by increased mechanical properties. Cell studies showed that cav-1 deficiency leads to increased osteoblast differentiation. These results suggest that cav-1 helps to maintain osteoblast progenitors in a less differentiated state. INTRODUCTION: The absence of caveolin-1 in cellular membranes causes dysregulated signaling. To understand the role of the caveolar microdomain in bone homeostasis, we examined the skeletal phenotype of 5- and 8-wk-old cav-1(-/-) mice. MATERIALS AND METHODS: High-resolution microCT imaging showed a region-specific effect of cav-1 deficiency on the skeleton. At 5 wk, cav-1(-/-) mice had increased epiphyseal bone volume (+58.4%, p = 0.05); at 8 wk, metaphyseal bone volume was increased by 77.4% (p = 0.008). Cortical bone at the femoral mid-diaphysis showed that the periosteal area of cav-1(-/-) mice significantly exceeded that of cav-1(+/+) mice by 23.9% and 16.3% at 5 and 8 wk, respectively, resulting in increased mechanical properties (I(max): +38.2%, p = 0.003 and I(mi): +23.7%, p = 0.03). RESULTS: Histomorphometry complemented microCT results showing increased bone formation rate (BFR) at trabecular and cortical sites at 5 wk, which supported findings of increased bone at 8 wk in cav-1(-/-) mice. Formal mechanical testing of the femoral diaphysis confirmed increased bone structure: stiffness increased 33% and postyield deflection decreased 33%. Stromal cells from cav-1(-/-) marrow showed a 23% increase in von Kossa-positive nodules; osteoclastogenesis was also modestly increased in cav-1-deficient marrow. Knockdown of cav-1 with siRNA in wildtype stromal cells increased alkaline phosphatase protein and expression of osterix and Runx2, consistent with osteoblast differentiation. CONCLUSIONS: These data suggest that cav-1 helps to maintain a less differentiated state of osteoblast progenitor cells, and the absence of cav-1 causes bone to mature more rapidly. Caveolin-1 may thus be a target for altering skeletal homeostasis.
机译：检查缺少小窝的cav-1（-/-）小鼠的骨骼表型。 muCT和组织学检查显示该基因缺失导致小梁和皮质骨增加。结构变化伴随着机械性能的提高。细胞研究表明cav-1缺乏导致成骨细胞分化增加。这些结果表明，cav-1有助于将成骨祖细胞维持在分化程度较低的状态。简介：细胞膜中不存在Caveolin-1会导致信号传导失调。为了了解caveolar微域在骨稳态中的作用，我们检查了5和8周龄cav-1（-/-）小鼠的骨骼表型。材料与方法：高分辨率microCT成像显示cav-1缺乏症对骨骼的区域特异性作用。在第5周，cav-1（-/-）小鼠的epi骨骨量增加（+ 58.4％，p = 0.05）;在第8周时，干phy端骨体积增加了77.4％（p = 0.008）。股骨中骨干的皮质骨显示，cav-1（-/-）小鼠的骨膜面积在5周和8周时分别比cav-1（+ / +）小鼠的骨膜面积分别大23.9％和16.3％，从而提高了机械性能（I（max）：+ 38.2％，p = 0.003，I（mi）：+ 23.7％，p = 0.03）。结果：组织形态计量学补充的microCT结果显示，在5周时小梁和皮质部位的骨形成率（BFR）增加，这支持在cav-1（-/-）小鼠中在8周时骨骼增加的发现。股骨干的正式机械测试证实骨骼结构增加：刚度增加了33％，屈服后挠度减少了33％。来自cav-1（-/-）骨髓的基质细胞显示von Kossa阳性结节增加23％。在缺乏cav-1的骨髓中，破骨细胞的生成也有所增加。在野生型基质细胞中用siRNA敲低cav-1可以增加碱性磷酸酶蛋白以及osterix和Runx2的表达，这与成骨细胞的分化一致。结论：这些数据表明，cav-1有助于维持成骨祖细胞的分化程度较低，而cav-1的缺失会导致骨骼更快地成熟。因此，Caveolin-1可能是改变骨骼稳态的靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号