...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemical Pharmacology >Carbon monoxide protects against ovariectomy-induced bone loss by inhibiting osteoclastogenesis
【24h】

Carbon monoxide protects against ovariectomy-induced bone loss by inhibiting osteoclastogenesis

机译：一氧化碳通过抑制破骨细胞形成来防止卵巢切除术引起的骨质流失

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

Carbon monoxide (CO) has been shown to have remarkable therapeutic value at low dosage by suppressing inflammation via inhibitory effects on macrophages, which are also precursors of osteoclasts (OC). The objective of the present study was to determine whether CO limits bone loss through its effects on osteoclastogenesis. Intraperitoneal injection of CO-releasing molecule 2 (CORM2) into mice with reduced bone mass due to ovariectomy (OVX) resulted in significantly elevated bone mass. Increased serum levels of collagen-type I fragments, tartrate-resistant acid phosphatase 5b, and reactive oxygen species (ROS) due to OVX were also decreased when treated with CORM2. In vitro, CORM2 inhibited receptor activator of nuclear factor-??B ligand (RANKL)-induced OC formation without affecting bone resorption. CORM2 reduced long-lasting ROS levels and nuclear factor-??B (NF-??B) activation in response to RANKL. Inhibition of NADPH oxidase partially reduced the inhibitory effect of CO. CO induced increase of peroxiredoxin 1 (PRX1) in BMM. Down-regulation of PRX1 reduced the inhibitory effect of CO on OC formation and sustained the ROS levels induced by RANKL, suggesting that CO reduces generation of ROS and scavenges ROS to inhibit osteoclastogenesis. These data suggest that the inhibitory effect of CO on osteoclastogenesis is caused by impaired RANKL signaling through defective NF-??B activation and reduced levels of long-lasting ROS. These changes result in decreased bone loss. Our data highlight the potential utility of CO for ameliorating bone loss induced by loss of ovarian function. ? 2013 Elsevier Inc.
机译：一氧化碳（CO）在低剂量下具有抑制巨噬细胞炎症的作用，该巨噬细胞也是破骨细胞（OC）的前体，具有抑制炎症的作用。本研究的目的是确定CO是否通过其对破骨细胞生成的作用来限制骨丢失。向卵巢切除术（OVX）导致骨量减少的小鼠腹腔注射CO释放分子2（CORM2）导致骨量显着增加。当用CORM2处理时，I型胶原蛋白片段，抗酒石酸酸性磷酸酶5b的血清水平升高以及由于OVX引起的活性氧（ROS）也降低了。在体外，CORM2抑制核因子-βB配体（RANKL）诱导的OC形成的受体激活剂，而不会影响骨吸收。响应RANKL，CORM2降低了持久的ROS水平和核因子-ΔB（NF-ΔB）活化。抑制NADPH氧化酶部分降低了CO的抑制作用。CO诱导了BMM中过氧化物酶1（PRX1）的增加。 PRX1的下调降低了CO对OC形成的抑制作用，并维持了RANKL诱导的ROS水平，表明CO减少了ROS的生成并清除了ROS，从而抑制了破骨细胞的生成。这些数据表明CO对破骨细胞的抑制作用是由于有缺陷的NF-κB活化和降低的长效ROS水平而导致的RANKL信号传导受损所致。这些变化导致骨质流失减少。我们的数据强调了CO改善卵巢功能丧失引起的骨质丢失的潜在效用。 ？ 2013爱思唯尔公司

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