Semaphorin-3a, neuropilin-1 and plexin-A1 in prosthetic-particle induced bone loss
Semaphorin-3a, neuropilin-1 and plexin-A1 in prosthetic-particle induced bone loss
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DOI：
10.1016/j.actbio.2015.11.025
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发表时间：
2016-01-15
影响因子：
9.7
通讯作者：
Haynes, D. R.
中科院分区：
文献类型：
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作者：
Saad, S.;Dharmapatni, A. A. S. S. K.;Haynes, D. R.
假体周围骨溶解(PPO)发生在假体磨损颗粒引起周围组织的炎症反应，从而导致随后的骨丢失。信号素-3a(Signaphorin-3a，SEM3A)、神经粘蛋白-1(Neuropilin-1，Nrp1)和神经丛蛋白-A1(Plexin-A1，PLEXA1)是近年来发现的调节骨代谢的轴突导向分子。本研究在体外研究了人PPO组织和聚乙烯颗粒(PE)刺激的人外周血单个核细胞(PBMC)来源的破骨细胞中SEM3A、Nrp1和PLEXA1的蛋白和mRNA的表达。此外，还评估了肿瘤坏死因子α对体外培养的破骨细胞的影响。在PPO组织中，在含有假体磨损颗粒的大的多核细胞内观察到SEM3A和Nrp1的颗粒染色模式。免疫荧光染色证实SEM3A、Nrp1和PLEXA1在体外培养的人大片多核破骨细胞中有表达。此外，在核因子kappaB受体激活剂配体(RANKL)诱导的破骨细胞分化过程中，SEM3A、Nrp1和PLEXA1的mRNA水平逐渐升高，PE颗粒的存在进一步增加了这三种分子的mRNA表达。用酶联免疫吸附试验检测第7天和第17天人破骨细胞培养上清液中可溶性SEM3A的含量。体外培养的人破骨细胞经肿瘤坏死因子α处理72 h后，SEM3A、Nrp1和PLEXA1基因的表达显著降低。我们的发现表明，SEM3A、Nrp1和PLEXA1可能在PPO中发挥重要作用，它们的相互作用，无论是单独的还是作为复杂的，可能在病理性骨丢失的进展中发挥作用。髋关节和膝关节置换术的速度每年至少增加5%。然而，这些关节置换的寿命是有限的，来自澳大利亚国家关节置换登记处的数据显示，全髋关节置换失败的主要原因是无菌性松动。在无菌松动中，假体释放出的磨损颗粒被巨噬细胞吞噬，导致炎性细胞因子的释放，并上调破骨细胞的形成和活性。信号素-3a、神经粘连蛋白-1和神经丛蛋白-A1是近年来发现的调节骨代谢的轴突导向分子。这是第一个表明这些分子可能与植入失败有关的报告。皇冠版权(C)2015由爱思唯尔有限公司代表Acta Materialia Inc.出版。保留所有权利。
Peri-prosthetic osteolysis (PPO) occurs in response to prosthetic wear particles causing an inflammatory reaction in the surrounding tissue that leads to subsequent bone loss. Semaphorin-3a (SEM3A), neuropilin-1 (NRP1) and plexin-A1 (PLEXA1) are axonal guidance molecules that have been recently implicated in regulating bone metabolism. This study investigated SEM3A, NRP1 and PLEXA1 protein and mRNA expression in human PPO tissue and polyethylene (PE) particle-stimulated human peripheral blood mononuclear cell (PBMC)-derived osteoclasts in vitro. In addition, the effects of tumour necrosis factor alpha (TNF alpha) on cultured osteoclasts was assessed. In PPO tissues, a granular staining pattern of SEM3A and NRP1 was observed within large multi-nucleated cells that contained prosthetic wear particles. Immunofluorescent staining confirmed the expression of SEM3A, NRP1 and PLEXA1 in large multi nucleated human osteoclasts in vitro. Furthermore, SEM3A, NRP1 and PLEXA1 mRNA levels progressively increased throughout osteoclast differentiation induced by receptor activator of nuclear factor kappa B ligand (RANKL), and the presence of PE particles further increased mRNA expression of all three molecules. Soluble SEM3A was detected in human osteoclast culture supernatant at days 7 and 17 of culture, as assessed by ELISA. TNF alpha treatment for 72 h markedly decreased the mRNA expression of SEM3A, NRP1 and PLEXA1 by human osteoclasts in vitro. Our findings suggest that SEM3A, NRP1 and PLEXA1 may have important roles in PPO, and their interactions, alone or as a complex, may have a role in pathological bone loss progression.Statement of SignificancePeri-prosthetic osteolysis occurs in response to prosthetic wear particles causing an inflammatory reaction in the surrounding tissue that leads to subsequent bone loss. The rate of hip and knee arthroplasty is increasing by at least 5% per year. However, these joint replacements have a finite lifespan, with data from the National Joint Replacement Registry (Australia) showing that the major cause of failure of total hip replacements is aseptic loosening. In aseptic loosening, wear particles liberated from prostheses are phagocytosed by macrophages, leading to release of inflammatory cytokines and up-regulation of osteoclast formation and activity. Semaphorin-3a, neuropilin-1 and plexin-A1 are axonal guidance molecules that have been recently implicated in regulating bone metabolism. This is the first report to show that these molecules may be involved in the implant failure. Crown Copyright (C) 2015 Published by Elsevier Ltd. on behalf of Acta Materialia Inc. All rights reserved.