• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell and Tissue Research >Endoplasmic reticulum stress-mediated inflammatory signaling pathways within the osteolytic periosteum and interface membrane in particle-induced osteolysis
【24h】

Endoplasmic reticulum stress-mediated inflammatory signaling pathways within the osteolytic periosteum and interface membrane in particle-induced osteolysis

机译：内质网应激介导的溶骨性骨膜和界面膜内的炎症诱导信号转导

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

Aseptic loosening secondary to periprosthetic inflammatory osteolysis results from the biological response to wear particles and is a leading cause of arthroplasty failure. The origin of this inflammatory response remains unclear. We aim to validate the definite link between endoplasmic reticulum (ER) stress and particle-induced inflammatory signaling pathways in periprosthetic osteolysis. We examine the histopathologic changes of osteolysis and the expression of specific biomarkers for ER-stress-mediated inflammatory signaling pathways (IRE1 alpha, GRP78/Bip, c-Fos, NF-kappa B, ROS and Ca2+). Moreover, pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) and osteoclastogenic molecules (VEGF, OPG, RANKL and M-CSF) were assessed in clinical interface membranes and murine periosteum tissues. We found wear particles to be capable of inducing ER stress in macrophages within clinical osteolytic interface membranes and murine osteolytic periosteum tissues and to be associated with the inflammatory response and osteoclastogenesis. Blocking ER stress with sodium 4-phenylbutyrate (4-PBA) results in a dramatic amelioration of particle-induced osteolysis and a significant reduction of ER-stress intensity. Simultaneously, this ER-stress blocker also lessens inflammatory cell infiltration, diminishes the capability of osteoclastogenesis and reduces the inflammatory response by lowering IRE1 alpha, GRP78/Bip, c-Fos, NF-kappa B, ROS and Ca2+ levels. Thus, ER stress plays an important role in particle-induced inflammatory osteolysis and osteoclastogenic reactions. The pharmacological targeting of ER-stress-mediated inflammatory signaling pathways might be an appealing approach for alleviating or preventing particle-induced osteolysis in at-risk patients.
机译：假体周围炎性骨溶解继发的无菌性松动是由对磨损颗粒的生物学反应引起的，并且是关节置换术失败的主要原因。这种炎症反应的起源尚不清楚。我们旨在验证假体周围骨质疏松症中内质网（ER）应力与颗粒诱导的炎症信号通路之间的明确联系。我们检查了骨溶解的组织病理学变化以及ER应激介导的炎症信号通路（IRE1α，GRP78 / Bip，c-Fos，NF-κB，ROS和Ca2 +）的特定生物标记物的表达。此外，在临床界面膜和鼠骨膜组织中评估了促炎性细胞因子（TNF-α，IL-1β和IL-6）和破骨细胞分子（VEGF，OPG，RANKL和M-CSF）。我们发现磨损颗粒能够在临床溶骨界面膜和小鼠溶骨性骨膜组织内的巨噬细胞中诱导内质网应激，并与炎症反应和破骨细胞发生有关。用4-苯基丁酸钠（4-PBA）阻止ER应激可显着改善颗粒诱导的骨溶解并显着降低ER应激强度。同时，这种ER应激阻滞剂还通过降低IRE1α，GRP78 / Bip，c-Fos，NF-κB，ROS和Ca2 +水平来减少炎症细胞浸润，破骨细胞生成能力并降低炎症反应。因此，内质网应激在颗粒诱导的炎症性骨溶解和破骨细胞反应中起重要作用。 ER应激介导的炎症信号通路的药理靶向可能是缓解或预防高危患者中颗粒诱导的骨溶解的一种有吸引力的方法。

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