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The pathogenesis of OA remains unclear and while many medications modify the disease's inflammatory components, no curative or reversal treatments exist. Identifying differentially abundant metabolites and proteins correlated with osteoarthritis severity could improve early diagnosis, track disease progression, and evaluate responses to interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify molecular markers of osteoarthritis severity based on histological and macroscopic grading.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>Cross\u2010sectional study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Post\u2010mortem synovial fluid was collected from 58 Thoroughbred racehorse joints and 83 joints from mixed breeds. Joints were histologically and macroscopically scored and categorised by OA and synovitis grade. Synovial fluid nuclear magnetic resonance metabolomic and mass spectrometry proteomic analyses were performed, individually and combined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In Thoroughbreds, synovial fluid concentrations of metabolites 2\u2010aminobutyrate, alanine and creatine were elevated for higher OA grades, while glutamate was reduced for both Thoroughbreds and mixed breeds. In mixed breeds, concentrations of three uncharacterised proteins, lipopolysaccharide binding protein and immunoglobulin kappa constant were lower for higher OA grades; concentrations of an uncharacterised protein were higher for OA grade 1 only, and apolipoprotein A1 concentrations were higher for OA grades 1 and 2 compared with lower grades. For Thoroughbreds, gelsolin concentrations were lower for higher OA grades, and afamin was lower at a higher synovitis grade. Correlation analyses of combined metabolomics and proteomics datasets revealed 58 and 32 significant variables for Thoroughbreds and mixed breeds, respectively, with correlations from \u22120.48 to 0.42 and \u22120.44 to 0.49.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Limitations<\/jats:title>\n                    <jats:p>The study's reliance on post\u2010mortem assessments limits correlation with clinical osteoarthritis severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Following stratification of equine OA severity through histological and macroscopic grading, synovial fluid metabolomic and proteomic profiling identified markers that may support earlier diagnosis and progression tracking. Further research is needed to correlate these markers with clinical osteoarthritis severity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/evj.14490","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:40:26Z","timestamp":1740012026000},"page":"1204-1218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Metabolomic and proteomic stratification of equine osteoarthritis"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0489-7997","authenticated-orcid":false,"given":"James R.","family":"Anderson","sequence":"first","affiliation":[{"name":"Musculoskeletal and Ageing Science Institute of Life Course and Medical Sciences, University of Liverpool  Liverpool UK"},{"name":"Veterinary Anatomy, Physiology and Pathology Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool  Liverpool 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