Statins attenuate polymethylmethacrylate-mediated monocyte activation
Statins attenuate polymethylmethacrylate-mediated monocyte activation
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DOI：
10.1080/17453670710014888
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发表时间：
2008-01-01
影响因子：
3.7
通讯作者：
Redmond, Paul H.
中科院分区：
文献类型：
--
作者：
Laing, Alan J.;Dillon, John P.;Redmond, Paul H.
假体周围溶骨导致假体部件无菌性松动，增加假体周围骨折的风险，并且由于大量骨质流失，使翻修手术复杂化，最终成为关节置换术失败的主要原因。HMG-CoA还原酶抑制剂属于他汀类药物家族，其抗炎特性已得到广泛认可。我们研究了在开始溶骨周期的第一阶段，即单核细胞激活中状态的可能作用。方法采用他汀类药物cerivastatin预处理细胞后，建立人单核细胞/巨噬细胞对聚甲基丙烯酸甲酯（PMMA）颗粒炎症反应的体外模型。分析基于TNF-和MCP-1细胞因子产生的细胞活化，并使用western blot分析评估细胞内Raf-MEK-ERK信号转导通路，以确定其在细胞活化和观察到的cerivastatin效应中的作用。结果我们发现，cerivastatin预处理可显著抑制人单核细胞对聚甲基丙烯酸甲酯颗粒激活的炎性细胞因子TNF-和MCP-1的产生。这种炎症激活和衰减似乎是通过细胞内Raf-MEK-ERK途径介导的。我们提出，通过干预上游激活阶段，随后的破骨细胞激活和骨溶解可以被抑制。我们认为，他汀类药物的抗炎特性可能在无菌性松动的情况下发挥潜在的预防作用，从而延长种植体的寿命。
Background Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation.Methods We used an in vitro model of the human monocyte/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF- and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed.Results We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF- and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway.Interpretation We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.