UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease
UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease
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DOI：
10.1080/17453670510041321
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发表时间：
2005-06-01
影响因子：
3.7
通讯作者：
Goodman, SB
中科院分区：
文献类型：
--
作者：
Epstein, NJ;Bragg, WE;Goodman, SB
背景我们在一种新的小鼠模型中检测了超高分子量聚乙烯（UHMWPE）颗粒对单核细胞促炎基因表达的影响。我们假设肿瘤坏死因子-α的单核细胞基因转录（TNF-α）、白细胞介素-1 β（IL-1 β），白细胞介素-6（IL-6）和巨噬细胞趋化蛋白-1（MCP-1）将通过在该鼠髓内杆模型中添加聚乙烯颗粒而上调。在C57 bl/6小鼠的双侧股骨中，此外，右侧股骨注射了3 x 10（9）个UHMWPE颗粒。在术后2、4和10周通过骨髓抽吸和Ficoll-Paque离心分离单核骨髓细胞。分离总RNA并进行实时RT-PCR以定量基因表达。组织学标本也进行了分析，以跟踪假体周围tissue. Results颗粒的变化，UHMWPE刺激单核细胞的基因转录时，检查在术后2，4和10周，相比，棒组。IL-1 β和MCP-1 mRNA的相对水平在10周的时间过程中以线性方式增加。IL-6 mRNA表达增强，4周达高峰。TNF-α mRNA的表达是可变的，并在4周时达到最低值。UHMWPE颗粒的加入刺激巨噬细胞和巨噬细胞来源的多核细胞进入骨-植入物界面.Interpretation在该模型中，单团UHMWPE颗粒对单核细胞的基因转录产生长期影响，从而使慢性炎症状态永久化。这种髓内颗粒诱导炎症的小鼠模型模拟了与人类植入物磨损相关的假体周围事件，并可能有助于对磨损碎屑相关假体失效进行更深入的机械理解。
Background We examined the effects of ultra-high molecular weight polyethylene (UHMWPE) particles on mononuclear cell proinflammatory gene expression in a novel murine model. We hypothesized that mononuclear cell gene trainscription of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1) would be upregulated by the addition of polyethylene particles in this murine intramedullary rod model.Material and methods The model involved a stainless steel Kirschner wire inserted retrograde with a line-toline fit in bilateral femora of C57bl/6 mice. Additionally, the right femora were injected with 3 x 10(9) UHMWPE particles. Mommuclear marrow cells were isolated by bone marrow aspiration and Ficoll-Paque centrifugation at 2, 4 and 10 weeks post-surgery. Total RNA was isolated and real-time RT-PCR was performed to quantify gene expression. Histological specimens of explanted femora were also analyzed to track the changes in periprosthetic tissue.Results UHMWPE particles stimulated gene transcription in mommuclear cells when examined at 2, 4 and 10 weeks post-surgery, compared to the rod-only group. Relative levels of IL-1 beta and MCP-1 mRNA increased in a linear fashion over the 10-week time-course. IL-6 mRNA showed increased expression which peaked at 4 weeks. TNF-alpha mRNA expression was variable and reached a minimum at 4 weeks. The addition of UHMWPE particles stimulated ingress of macrophages and multinuclear cells of macrophage origin to the bone-implant interface.Interpretation In this model, a single bolus of UHMWPE particles had a long-term effect on gene transcription in monomuclear cells which perpetuated a chronic inflammatory state. This murine model of intramedullary particle-induced inflammation simulates periprosthetic events associated with implant wear in humans, and may contribute to a more mechanistic understanding of wear-debris associated prosthesis failure.