Metformin suppresses UHMWPE particle-induced osteolysis in the mouse calvaria by promoting polarization of macrophages to an anti-inflammatory phenotype.
Metformin suppresses UHMWPE particle-induced osteolysis in the mouse calvaria by promoting polarization of macrophages to an anti-inflammatory phenotype.
复制标题
二甲双胍通过促进巨噬细胞极化至抗炎表型来抑制 UHMWPE 颗粒诱导的小鼠颅骨骨溶解
DOI：
10.1186/s10020-018-0013-x
复制
发表时间：
2018-05-09
期刊：
影响因子：
--
通讯作者：
Cao X
中科院分区：
文献类型：
--
作者：
Yan Z;Tian X;Zhu J;Lu Z;Yu L;Zhang D;Liu Y;Yang C;Zhu Q;Cao X
植物失败仍然是通过TJA成功治疗的主要障碍。假体周围骨溶解和无菌性松动被认为是磨损碎片引起的局部调节机制中断的证据，与骨溶解相关的过度骨吸收和骨-假体界面损伤有关。因此，迫切需要探索限制和治疗假体周围骨溶解和无菌性松动的策略。方法观察小鼠原代骨髓巨噬细胞（BMMs）暴露于超高分子量聚乙烯（UHMWPE）颗粒和不同浓度的二甲双胍（加或不加5-氨基咪唑-4-羧酰胺核糖核苷）对AMPK的激活或抑制作用。采用小鼠颅骨模型研究二甲双胍对UHMWPE颗粒诱导的骨溶解的体内影响。结果小鼠原代BMMs颗粒分泌较多促炎细胞因子、肿瘤坏死因子-α和白细胞介素-6。二甲双胍治疗可抑制这些变异，并促进具有抗炎能力的细胞因子IL-10的释放。在体内，二甲双胍减少了促炎细胞因子、破骨细胞生成和骨溶解的产生，增加了IL-10的产生。二甲双胍还通过激活AMPK，在体内促进巨噬细胞极化至抗炎表型。限制和纠正假体周围骨溶解和无菌性松动的一个关键点是抑制炎症因子的产生和活化的巨噬细胞诱导的破骨细胞活化。二甲双胍减轻颗粒引起的小鼠颅骨骨溶解的能力与破骨细胞数量减少和巨噬细胞极化到抗炎功能表型有关。结论二甲双胍可抑制种植体碎片所致的骨溶解。因此，我们假设二甲双胍可能是一种潜在的药物，用于治疗由种植体碎片引起的骨溶解。
BackgroundImplant failure remains a major obstacle to successful treatment via TJA. Periprosthetic osteolysis and aseptic loosening are considered as proof of wear debris-induced disruption of local regulatory mechanisms related to excessive bone resorption associated with osteolysis and the damage at the bone-prosthesis interface. Therefore, there is an immediate need to explore strategies for limiting and curing periprosthetic osteolysis and aseptic loosening.MethodsWe analyzed the in vitro cytokine production by primary mouse bone marrow macrophages (BMMs) that were exposed to ultra-high molecular weight polyethylene (UHMWPE) particles and treated with metformin at different concentrations with or without 5-aminoimidazole-4-carboxamide ribonucleoside to activate or inhibit AMPK. A mouse calvarial model was used to examine the in vivo effects of metformin on UHMWPE particle-induced osteolysis.ResultsWith particles, primary mouse BMMs secreted more pro-inflammatory cytokines tumor necrosis factor-α and interleukin (IL)-6. Treatment with metformin inhibited these variations and promoted the release of cytokine IL-10 with anti-inflammatory capability. In vivo, metformin reduced the production of pro-inflammatory cytokines, osteoclastogenesis, and osteolysis, increasing IL-10 production. Metformin also promoted the polarization of macrophages to an anti-inflammatory phenotype in vivo via AMPK activation.DiscussionA crucial point in limiting and correcting the periprosthetic osteolysis and aseptic loosening is the inhibition of inflammatory factor production and osteoclast activation induced by activated macrophages. The ability of metformin to attenuate osteolysis induced in mouse calvaria by the particles was related to a reduction in osteoclast number and polarization of macrophages to an anti-inflammatory functional phenotype.ConclusionsMetformin could limit the osteolysis induced by implant debris. Therefore, we hypothesized that metformin could be a potential drug for osteolysis induced by implant debris.
登录
查看更多内容
影响因子：
6.4
作者：
Davies LC;Taylor PR
通讯作者：
Taylor PR
影响因子：
4.8
作者：
Patel, Vimal A.;Massenburg, Donald;Levine, Jerrold S.
通讯作者：
Levine, Jerrold S.
影响因子：
--
作者：
Malyshev I;Malyshev Y
通讯作者：
Malyshev Y
影响因子：
4.9
作者：
Nich C;Langlois J;Marchadier A;Vidal C;Cohen-Solal M;Petite H;Hamadouche M
通讯作者：
Hamadouche M
影响因子：
16.2
作者：
Monami, Matteo;Cresci, Barbara;Mannucci, Edoardo
通讯作者：
Mannucci, Edoardo