Schadzek Patrik, Derksen Alexander, Behrens Wiebke, Kosanke Maike, Dittrich-Breiholz Oliver, Hamm Anika, Elger Kirsten, Roger Yvonne, Yang Ines, Stiesch Meike, Noll Yvonne, Haertlé Marco, Tuecking Lars-René, Stukenborg-Colsman Christina, Windhagen Henning, Tran Doan Duy Hai, Melk Anette, Hoffmann Andrea
Department of Orthopaedic Surgery, Biological Basics for Biohybrid Implants OE 8893, Hannover Medical School, Anna-von-Borries-Str. 1-7, Stadtfelddamm 34, 30625, Hannover, Germany.
Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625, Hannover, Germany.
Sci Rep. 2025 Sep 12;15(1):32419. doi: 10.1038/s41598-025-13922-3.
Endoprosthesis loosening is the major cause of arthroplasty failure. Currently, radiography, histo-pathological classification of the periprosthetic membrane, and microbiological examination are used retrospectively for diagnosis. Prospective options for early diagnosis are not available. The study presented here aimed to identify (prospective) molecular biomarkers of implant loosening in tissue samples from patients. Four patient cohorts (primary and revision arthroplasty due to aseptic loosening of hip or knee) were defined. Aseptic loosening of implants was assessed by the standardised approach of the Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. Synovial fluid, bone marrow, and blood were collected from 96 patients. Mesenchymal stromal cells (BM-MSCs) were isolated from the bone marrow. Bulk RNA-sequencing of 28 samples (including a fifth patient cohort with knee arthrofibrosis as aseptic cause for revision surgery) showed that Glycoprotein Non-Metastatic Melanoma Protein B mRNA (GPNMB) was significantly upregulated in BM-MSCs derived from revision patients compared to patients with primary implantations. Elevated GPNMB mRNA levels were confirmed with qRT-PCR. Synovial fluid plasma study by ELISA revealed increased levels of GPNMB protein in patients undergoing revision surgery compared to patients undergoing primary arthroplasty. GPNMB concentration in synovial fluid plasma, which can be obtained non-invasively, could be a potential biomarker for early detection of implant loosening, ahead of current diagnostic procedures.
人工关节假体松动是关节置换术失败的主要原因。目前，X线摄影、假体周围膜的组织病理学分类以及微生物学检查用于回顾性诊断。尚无早期诊断的前瞻性方法。本文介绍的研究旨在识别（前瞻性地）患者组织样本中植入物松动的分子生物标志物。定义了四个患者队列（因髋关节或膝关节无菌性松动进行初次和翻修关节置换术）。通过膝关节协会全膝关节置换术X线评估和评分系统的标准化方法评估植入物的无菌性松动。从96例患者中收集滑液、骨髓和血液。从骨髓中分离间充质基质细胞（BM-MSC）。对28个样本（包括第五个患者队列，该队列以膝关节纤维性关节病作为翻修手术的无菌原因）进行的批量RNA测序显示，与初次植入患者相比，翻修患者来源的BM-MSC中糖蛋白非转移性黑色素瘤蛋白B mRNA（GPNMB）显著上调。通过qRT-PCR证实GPNMB mRNA水平升高。ELISA法进行的滑液血浆研究显示，与初次关节置换术患者相比，翻修手术患者的GPNMB蛋白水平升高。滑液血浆中的GPNMB浓度可通过非侵入性方法获得，在当前诊断程序之前，它可能是早期检测植入物松动的潜在生物标志物。
