{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:39:40Z","timestamp":1791686380859,"version":"4.3.4"},"reference-count":27,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan of the Republic of Bulgaria","award":["BG-RRP-2.004-0007-C01"],"award-info":[{"award-number":["BG-RRP-2.004-0007-C01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Distinguishing between osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) remains challenging despite different underlying mechanisms. Synovial fluid reflects metabolic changes within affected joints, yet comprehensive metabolomic comparisons across these conditions are limited. We aimed to identify disease-specific metabolic signatures in synovial fluid that could improve differential diagnosis and reveal therapeutic targets. Methods: We collected synovial fluid from 39 patients (20 OA, 5 RA, and 14 PsA) during routine knee arthrocentesis between January 2023 and February 2024. Following metabolite extraction, we performed untargeted metabolomic profiling using quadrupole time-of-flight liquid chromatography\u2013mass spectrometry (Q-TOF LC\/MS). Data underwent multivariate statistical analysis, including principal component analysis (PCA) and partial least squares\u2013discriminant analysis (PLS-DA), to identify discriminatory metabolites. Results: While unsupervised analysis showed overlap between groups, supervised PLS-DA achieved clear metabolic separation. RA samples showed elevated itaconic acid, indicating inflammatory macrophage activation, and increased O-acetylserine, suggesting altered one-carbon metabolism. Hypoxanthine was decreased, which reflected severe metabolic stress. PsA exhibited the unique elevation of 4,4-dimethylcholestane and 2-oxoarginine. These metabolites have previously been unreported in this disease. OA demonstrated increased hippuric acid and indoleacetic acid, which are both gut microbiota products, supporting the gut\u2013joint axis hypothesis. Conclusions: Each arthritis type displayed distinct metabolic fingerprints in synovial fluid. Candidate discriminatory metabolites, including gut-derived metabolites in OA and specific lipid alterations in PsA, open new diagnostic and therapeutic avenues. Given the limited RA sample size (n = 5), RA-related results should be viewed as exploratory and requiring validation in larger independent cohorts. These metabolites may, after rigorous validation in larger and independent cohorts, contribute to multi-metabolite biomarker panels for earlier diagnosis and to the rational design of targeted therapeutics addressing disease-specific metabolic disruptions.<\/jats:p>","DOI":"10.3390\/metabo16010070","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:17:32Z","timestamp":1768292252000},"page":"70","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synovial Joint Fluid Metabolomic Profiles and Pathways Differentiate Osteoarthritis, Rheumatoid Arthritis, and Psoriatic Arthritis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7429-9349","authenticated-orcid":false,"given":"Ozan","family":"Kaplan","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8030-0529","authenticated-orcid":false,"given":"Rositsa","family":"Karalilova","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Clinic of Rheumatology, University Hospital Kaspela, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zguro","family":"Batalov","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Clinic of Rheumatology, University Hospital Kaspela, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Batalov","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Clinic of Rheumatology, University Hospital Kaspela, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Research Institute at Medical University of Plovdiv, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1501-0175","authenticated-orcid":false,"given":"Victoria","family":"Sarafian","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Research Institute at Medical University of Plovdiv, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine","family":"Ko\u00e7","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-5512","authenticated-orcid":false,"given":"Mustafa","family":"\u00c7elebier","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-3541","authenticated-orcid":false,"given":"Feza","family":"Korkusuz","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Faculty of Medicine, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1007\/s10787-025-01833-8","article-title":"Rethinking arthritis: Exploring its types and emerging management strategies","volume":"33","author":"Britto","year":"2025","journal-title":"Inflammopharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s40744-021-00365-1","article-title":"Differentiating Psoriatic Arthritis from Osteoarthritis and Rheumatoid Arthritis: A Narrative Review and Guide for Advanced Practice Providers","volume":"8","author":"Saalfeld","year":"2021","journal-title":"Rheumatol. 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