Glycoprotein non-metastatic melanoma protein B is a potential biomarker for arthroplasty aseptic loosening

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.