Neuerburg Carl, Loer Theresa, Mittlmeier Lena, Polan Christina, Farkas Zsuzsanna, Holdt Lesca Miriam, Utzschneider Sandra, Schwiesau Jens, Grupp Thomas M, Böcker Wolfgang, Aszodi Attila, Wedemeyer Christian, Kammerlander Christian
Experimental Surgery and Regenerative Medicine, Department of General, Trauma and Reconstructive Surgery, Munich University Hospital LMU, Munich, Germany.
Department of Orthopedics and Trauma Surgery, University Hospital, University of Duisburg-Essen, Essen, Germany.
Int J Mol Med. 2016 Dec;38(6):1652-1660. doi: 10.3892/ijmm.2016.2780. Epub 2016 Oct 18.
Aseptic loosening mediated by wear particle-induced osteolysis (PIO) remains the major cause of implant loosening in endoprosthetic surgery. The development of new vitamin E (α-tocopherol)-blended ultra-high molecular weight polyethylene (VE-UHMWPE) with increased oxidation resistance and improved mechanical properties has raised hopes. Furthermore, regenerative approaches may be opened, as vitamin E supplementation has shown neuroprotective characteristics mediated via calcitonin gene-related peptide (CGRP), which is known to affect bone remodeling in PIO. Therefore, the present study aimed to further clarify the impact of VE-UHMWPE wear particles on the osseous microenvironment and to identify the potential modulatory pathways involved. Using an established murine calvaria model, mice were subjected to sham operation (SHAM group), or treated with UHMWPE or VE-UHMWPE particles for different experimental durations (7, 14 and 28 days; n=6/group). Morphometric analysis by micro-computed tomography detected significant (p<0.01) and comparable signs of PIO in all particle-treated groups, whereas markers of inflammation [tumor necrosis factor (TNF)-α/tartrate resistant acid phosphatase (TRAP) staining] and bone remodeling [Dickkopf-related protein 1 (DKK-1)/osteoprotegerin (OPG)] were most affected in the early stages following surgery. Taking the present data into account, VE-UHMWPE appears to have a promising biocompatibility and increased ageing resistance. According to the α-CGRP serum levels and immunohistochemistry, the impact of vitamin E on neuropeptidergic signaling and its chance for regenerative approaches requires further investigation.
磨损颗粒诱导的骨溶解(PIO)介导的无菌性松动仍然是假体手术中植入物松动的主要原因。新型维生素E(α-生育酚)共混的超高分子量聚乙烯(VE-UHMWPE)具有更高的抗氧化性和改善的机械性能,这带来了新的希望。此外,由于补充维生素E已显示出通过降钙素基因相关肽(CGRP)介导的神经保护特性,而CGRP已知会影响PIO中的骨重塑,因此可能会开辟再生方法。因此,本研究旨在进一步阐明VE-UHMWPE磨损颗粒对骨微环境的影响,并确定其中涉及的潜在调节途径。使用已建立的小鼠颅骨模型,对小鼠进行假手术(假手术组),或用UHMWPE或VE-UHMWPE颗粒处理不同的实验持续时间(7、14和28天;每组n = 6)。通过微计算机断层扫描进行的形态计量分析在所有颗粒处理组中均检测到显著(p<0.01)且相当的PIO迹象,而炎症标志物[肿瘤坏死因子(TNF)-α/抗酒石酸酸性磷酸酶(TRAP)染色]和骨重塑标志物[Dickkopf相关蛋白1(DKK-1)/骨保护素(OPG)]在手术后的早期受到的影响最大。考虑到目前的数据,VE-UHMWPE似乎具有良好的生物相容性和更高的抗老化性。根据α-CGRP血清水平和免疫组织化学,维生素E对神经肽能信号传导的影响及其用于再生方法的可能性需要进一步研究。