期刊
OSTEOARTHRITIS AND CARTILAGE
卷 29, 期 1, 页码 124-133出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2020.09.005
关键词
Synovial fluid; Knee joint; Tissue-dependent; Biomarker; Osteoarthritis; Proteomics
资金
- Wellcome Trust Intermediate Clinical Fellowship [107471/Z/15/Z]
- Dutch Arthritis Society [LLP14]
- Maastricht University Medical Center
- Annadal Foundation
- EU-FP7 HEALTH.2012.2.4.5-2 (D-BOARD) [305815]
- START-Program of the Faculty of Medicine of the RWTH Aachen
- MRC and vs Arthritis as part of the Medical Research Council vs Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA) [MR/R502182/1]
This study identified tissue-dependent secreted proteins from intra-articular human knee osteoarthritis tissues, which may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis.
Objective: For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis. Design: Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation. Results: Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid revealed 70 proteins with a relatively higher abundance and 264 proteins with a relatively lower abundance in osteoarthritic synovial fluid. Of the 70 higher abundance proteins, 23 were amongst the most highly expressed in the secretomes of a specific intra-articular tissue measured. Tissue-dependent release was validated for SLPI, C8, CLU, FN1, RARRES2, MATN3, MMP3 and TNC. Abundance in synovial fluid of tissue-dependent proteins was validated for IGF2, AHSG, FN1, CFB, KNG and C8. Conclusions: We identified proteins with a tissue-dependent release from intra-articular human knee OA tissues. A number of these proteins also had an osteoarthritis-specific abundance in knee synovial fluid. These proteins may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
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