Department of Orthopedic Surgery, Hokkaido University, Faculty of Medicine and Graduate School of Medicine, Kita-15, Nish-7, Kita-ku, Sapporo 060-8638, Japan; Global Institution for Collaborative Research and Education (GI-CoRE), Frontier Research Center for Advanced Material and Life Science Bldg No 2, Hokkaido University, Japan.
Department of Orthopedic Surgery, Hokkaido University, Faculty of Medicine and Graduate School of Medicine, Kita-15, Nish-7, Kita-ku, Sapporo 060-8638, Japan.
Acta Biomater. 2019 Apr 15;89:242-251. doi: 10.1016/j.actbio.2019.03.028. Epub 2019 Mar 14.
Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant.
维生素 E 共混超高分子量聚乙烯（VE-UHMWPE）是一种新引入的用于假体部件的材料，已被证明在实验动物模型中具有比传统聚乙烯更好的机械性能和更少的不良细胞反应。然而，VE-UHMWPE 颗粒引发降低溶骨性活性的机制尚不清楚，仍需进一步研究。因此，本研究旨在探索与 VE-UHMWPE 颗粒相关的可能的抗溶骨性机制。对 VE-UHMWPE 颗粒刺激的人巨噬细胞进行转录谱分析和生物信息学分析显示，与 UHMWPE 颗粒刺激的巨噬细胞相比，巨噬细胞的转录程序明显不同。在上调基因中，发现与 UHMWPE 颗粒相比，用 VE-UHMWPE 颗粒培养的巨噬细胞中 IL-27 显著升高（p=0.0084）。此外，我们研究了 IL-27 在溶骨性小鼠模型中的潜在抗溶骨性功能。有趣的是，将重组 IL-27 施用于颅骨可显著减轻 UHMWPE 颗粒引发的溶骨性病变（p=0.0002）。同样，IL-27 抑制了体外常规 UHMWPE 颗粒诱导的破骨细胞分化（p=0.0116）和炎症反应（p<0.0001）。这是第一项证明 IL-27 参与巨噬细胞对 VE-UHMWPE 颗粒的反应及其在溶骨性中的调节作用的研究。我们的数据突出了一种新的治疗剂，用于治疗由聚乙烯碎片引起的炎症性溶骨性疾病。意义声明：由于炎症性溶骨性松动仍然是关节置换失败的主要原因，也是全球巨大的经济负担。预防这种失败的理想方法应该是尽量减少植入物部位磨损颗粒引发的炎症反应。了解 VE-UHMWPE 颗粒与传统 UHMWPE 颗粒相比引发较少细胞反应和降低溶骨性的机制可能有助于发现调节因子。在本研究中，我们报道了 IL-27 是一种有效的炎症性溶骨性调节因子，参与了与 VE-UHMWPE 颗粒相关的降低生物活性和溶骨性潜力。在全关节置换术后体内启动 IL-27 的产生可能是延长植入物寿命的一种新策略。
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