Role of direct estrogen receptor signaling in wear particle-induced osteolysis.
Role of direct estrogen receptor signaling in wear particle-induced osteolysis.
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DOI：
10.1016/j.biomaterials.2012.10.030
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发表时间：
2013-01
期刊：
影响因子：
14
通讯作者：
Goodman, Stuart B.
中科院分区：
文献类型：
--
作者：
Nich, Christophe;Rao, Allison J.;Valladares, Roberto D.;Li, Chenguang;Christman, Jane E.;Antonios, Joseph K.;Yao, Zhenyu;Zwingenberger, Stefan;Petite, Herve;Hamadouche, Moussa;Goodman, Stuart B.
最近在小鼠颅骨模型中显示，手术卵巢切除术后雌激素停药可减轻颗粒诱导的骨溶解。目前，我们假设雌激素受体（ER）参与了这种矛盾的现象。为了检验这一假设，我们首先使用野生型 (WT) C57BL6J 雌性小鼠、ERα 缺陷 (ERαKO) 小鼠和用 17β-雌二醇 (E2) 或 ER 全拮抗剂 ICI 182,780 治疗的 WT 小鼠，在小鼠颅骨模型中评估了聚乙烯 (PE) 颗粒诱导的骨溶解。根据显微 CT 和组织形态计量学，我们发现与 WT 和 E2 组相比，ERαKO 和 ICI 182,780 治疗小鼠的骨吸收持续改变。然后，我们证明，内质网破坏持续降低了 PE 和聚甲基丙烯酸甲酯 (PMMA) 颗粒诱导的体外小鼠巨噬细胞 TNF-α 的产生。在 RAW 264.7 和 WT 巨噬细胞中使用 ICI 182,780 进行 ER 阻断后获得了类似的结果。相对于 WT 巨噬细胞或未处理的 RAW 细胞，ER 破坏和 ICI 182,780 预处理导致颗粒诱导的 TNF-α mRNA 表达持续下调。这些结果表明，作为巨噬细胞激活的一部分，雌性小鼠对磨损颗粒的反应涉及雌激素受体。雌激素受体可能被认为是颗粒诱导骨质溶解的未来治疗靶点。
Estrogen withdrawal following surgical ovariectomy was recently shown to mitigate particle-induced osteolysis in the murine calvarial model. Currently, we hypothesize that estrogen receptors (ERs) were involved in this paradoxical phenomenon. To test this hypothesis, we first evaluated polyethylene (PE) particle-induced osteolysis in the murine calvarial model, using wild type (WT) C57BL6J female mice, ERα deficient (ERαKO) mice, and WT mice either treated with 17β-estradiol (E2) or with the ER pan-antagonist ICI 182,780. According to micro-CT and histomorphometry, we showed that bone resorption was consistently altered in both ERαKO and ICI 182,780 treated mice as compared to WT and E2 groups. Then, we demonstrated that ER disruption consistently decreased both PE and polymethylmethacrylate (PMMA) particle-induced production of TNF-α by murine macrophages in vitro. Similar results were obtained following ER blockade using ICI 182,780 in RAW 264.7 and WT macrophages. ER disruption and pre treatment with ICI 182,780 resulted in a consistent down-regulation of particle-induced TNF-α mRNA expression relative to WT macrophages or untreated RAW cells. These results indicate that the response to wear particles involves estrogen receptors in female mice, as part of macrophage activation. Estrogen receptors may be considered as a future therapeutic target for particle-induced osteolysis.
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影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
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