PMID- 32407894 OWN - NLM STAT- MEDLINE DCOM- 20210726 LR - 20210927 IS - 1522-9653 (Electronic) IS - 1063-4584 (Print) IS - 1063-4584 (Linking) VI - 28 IP - 8 DP - 2020 Aug TI - Proteomic comparison of osteoarthritic and reference human menisci using data-independent acquisition mass spectrometry. PG - 1092-1101 LID - S1063-4584(20)30994-8 [pii] LID - 10.1016/j.joca.2020.05.001 [doi] AB - OBJECTIVE: Recent research in knee osteoarthritis (OA) highlights the role of the meniscus in OA pathology. Our aim was to compare the proteomes of medial and lateral menisci from end-stage medial compartment knee OA patients, with reference menisci from knee-healthy deceased donors, using mass spectrometry. DESIGN: Tissue plugs of O3 mm were obtained from the posterior horns of the lateral and medial menisci from one knee of 10 knee-healthy deceased donors and 10 patients undergoing knee replacement. Proteins were extracted and prepared for mass spectrometric analysis. Statistical analysis was conducted on abundance data that was log(2)-transformed, using a linear mixed effects model and evaluated using pathway analysis. RESULTS: We identified a total of 835 proteins in all samples, of which 331 were included in the statistical analysis. The largest differences could be seen between the medial menisci from OA patients and references, with most proteins showing higher intensities in the medial menisci from OA patients. Several matrix proteins, e.g., matrix metalloproteinase 3 (MMP3) (4.3 times higher values [95%CI 1.8, 10.6]), TIMP1 (3.5 [1.4, 8.5]), asporin (4.1 [1.7, 10.0]) and versican (4.4 [1.8, 10.9]), all showed higher abundance in medial menisci from OA patients compared to medial reference menisci. OA medial menisci also showed increased activation of several pathways involved in inflammation. CONCLUSION: An increase in protein abundance for proteins such as MMP and TIMP1 in the medial menisci from OA patients suggests simultaneous activation of both catabolic and anabolic processes that warrants further attention. CI - Copyright (c) 2020 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Folkesson, E AU - Folkesson E AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden; Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Rheumatology and Molecular Skeletal Biology, Lund, Sweden. Electronic address: elin.folkesson@med.lu.se. FAU - Turkiewicz, A AU - Turkiewicz A AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden. FAU - Ali, N AU - Ali N AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden. FAU - Ryden, M AU - Ryden M AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden. FAU - Hughes, H V AU - Hughes HV AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden. FAU - Tjornstrand, J AU - Tjornstrand J AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden; Department of Orthopaedics, Skane University Hospital, Lund, Sweden. FAU - Onnerfjord, P AU - Onnerfjord P AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Rheumatology and Molecular Skeletal Biology, Lund, Sweden. FAU - Englund, M AU - Englund M AD - Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, USA. LA - eng GR - 771121/ERC_/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200511 PL - England TA - Osteoarthritis Cartilage JT - Osteoarthritis and cartilage JID - 9305697 RN - 0 (ASPN protein, human) RN - 0 (Extracellular Matrix Proteins) RN - 0 (TIMP1 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (VCAN protein, human) RN - 126968-45-4 (Versicans) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Case-Control Studies MH - Extracellular Matrix Proteins/*metabolism MH - Female MH - Humans MH - Inflammation/*metabolism MH - Male MH - Mass Spectrometry MH - Matrix Metalloproteinase 3/metabolism MH - Menisci, Tibial/*metabolism MH - Middle Aged MH - Osteoarthritis, Knee/*metabolism MH - *Proteomics MH - Tissue Inhibitor of Metalloproteinase-1/metabolism MH - Versicans/metabolism PMC - PMC7397514 OTO - NOTNLM OT - Extracellular matrix OT - Mass spectrometry OT - Meniscus OT - Osteoarthritis EDAT- 2020/05/15 06:00 MHDA- 2021/07/27 06:00 PMCR- 2020/08/01 CRDT- 2020/05/15 06:00 PHST- 2020/01/30 00:00 [received] PHST- 2020/04/09 00:00 [revised] PHST- 2020/05/01 00:00 [accepted] PHST- 2020/05/15 06:00 [pubmed] PHST- 2021/07/27 06:00 [medline] PHST- 2020/05/15 06:00 [entrez] PHST- 2020/08/01 00:00 [pmc-release] AID - S1063-4584(20)30994-8 [pii] AID - 10.1016/j.joca.2020.05.001 [doi] PST - ppublish SO - Osteoarthritis Cartilage. 2020 Aug;28(8):1092-1101. doi: 10.1016/j.joca.2020.05.001. Epub 2020 May 11.