{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:18:32Z","timestamp":1787498312030,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2017\/12815-0"],"award-info":[{"award-number":["2017\/12815-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2017\/14460-4"],"award-info":[{"award-number":["2017\/14460-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Rio de Janeiro Research Foundation","award":["2017\/12815-0"],"award-info":[{"award-number":["2017\/12815-0"]}]},{"name":"Rio de Janeiro Research Foundation","award":["E-26\/201.259\/2021"],"award-info":[{"award-number":["E-26\/201.259\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Osteoarthritis (OA) is a degenerative joint disease that affects humans and animals worldwide. Its early diagnosis remains challenging due to subtle clinical signs and late radiographic changes. This study aimed to explore candidate biomarkers associated with spontaneous OA and to investigate their correlation with ultrasonographic scores to support early diagnosis. Clinical, radiographic, and ultrasonographic evaluations were performed on 52 equine metacarpophalangeal joints, with and without OA, allowing joint scoring and classification into osteoarthritis (OAG) and control groups. Synovial fluid samples were analyzed for cartilage degradation (C2C), untargeted 1H NMR-based metabolomics, and lipid peroxidation (TBARS). Statistical analyses included Student\u2019s t-test, Mann\u2013Whitney U test, univariate and multivariate metabolomic analyses, and Spearman\u2019s correlation (p &lt; 0.05). Ultrasonography revealed higher scores in the synovial fold, membrane, and fluid, indicating synovitis as the predominant finding in the acute phase. C2C and TBARS concentrations were significantly higher in the OAG. Seven metabolites differed between groups, with citrate and TBARS showing the strongest correlations with ultrasonographic scores. These findings suggest increased metabolic activity and lipid peroxidation in early OA and highlight citrate and TBARS as potential auxiliary biomarkers for early diagnosis associated with synovitis.<\/jats:p>","DOI":"10.3390\/vetsci13020140","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:00:33Z","timestamp":1770022833000},"page":"140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ultrasonographic Evidence of Synovitis Correlates with Synovial Citrate and TBARS in Equine Osteoarthritis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1243-5939","authenticated-orcid":false,"given":"Anna Paula","family":"Barreira","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, Veterinary Institute, Rural Federal University of Rio de Janeiro (UFRRJ), Seropedica 23890-000, Brazil"},{"name":"Postgraduate Program in Animal Biotechnology, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP), Botucatu 18618-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4328-6049","authenticated-orcid":false,"given":"Tha\u00eds","family":"Moreira","sequence":"additional","affiliation":[{"name":"Veterinary Institute, Rural Federal University of Rio de Janeiro (UFRRJ), Seropedica 23890-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Silva","sequence":"additional","affiliation":[{"name":"Veterinary Institute, Rural Federal University of Rio de Janeiro (UFRRJ), Seropedica 23890-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia","family":"Nunes","sequence":"additional","affiliation":[{"name":"Veterinary Institute, Rural Federal University of Rio de Janeiro (UFRRJ), Seropedica 23890-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Lioi","sequence":"additional","affiliation":[{"name":"Brazilian Jockey Club (JCB), Rio de Janeiro 22470-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kraus","sequence":"additional","affiliation":[{"name":"Brazilian Jockey Club (JCB), Rio de Janeiro 22470-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0540-9932","authenticated-orcid":false,"given":"Vittoria","family":"Altheman","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Animal Biotechnology, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP), Botucatu 18618-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8102-1941","authenticated-orcid":false,"given":"Marcela","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Animal Biotechnology, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP), Botucatu 18618-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Leite","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Veterinary Medicine, Rural Federal University of Rio de Janeiro (UFRRJ), Seropedica 23890-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-5856","authenticated-orcid":false,"given":"Andreza","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, Veterinary Institute, Rural Federal University of Rio de Janeiro (UFRRJ), Seropedica 23890-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-2775","authenticated-orcid":false,"given":"Fernando","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, Veterinary Institute, Rural Federal University of Rio de Janeiro (UFRRJ), Seropedica 23890-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilson","family":"Santos Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics (LabMet), Department of Genetics, State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-013, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7123-8265","authenticated-orcid":false,"given":"Daniel","family":"Lessa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Veterinary Clinic, Federal Fluminense University, Niteroi 24230-340, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Liz","family":"Alves","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Animal Biotechnology, Regenerative Medicine Lab, School of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP), Botucatu 18618-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/j.joca.2015.02.009","article-title":"Inflammatory biomarkers in osteoarthritis","volume":"23","author":"Daghestani","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_2","unstructured":"McIlwraith, C.W., Frisbie, C.D., Kawcak, C.E., and Van Weeren, R.P. (2016). Joint Disease in the Horse, Elsevier. [2nd ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e6485","DOI":"10.1590\/1414-431x20176485","article-title":"Metabolomics as a promising tool for early osteoarthritis diagnosis","volume":"50","author":"Duarte","year":"2017","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/art.20051","article-title":"Osteoarthritis: Is it a disease of cartilage or of bone?","volume":"50","author":"Felson","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00167-011-1705-8","article-title":"Biological aspects of early osteoarthritis","volume":"20","author":"Madry","year":"2012","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5574582","DOI":"10.1155\/2021\/5574582","article-title":"Biomarkers of joint damage in osteoarthritis: Current status and future directions","volume":"2021","author":"Kumavat","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.joca.2015.02.023","article-title":"Joint-dependent response to impact and implications for post-traumatic osteoarthritis","volume":"23","author":"Novakofski","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_8","first-page":"466","article-title":"Pro-inflammatory biomarkers and cytokines","volume":"14","author":"Dwivedi","year":"2023","journal-title":"J. Pharm. Negat. Results"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.tvjl.2008.01.017","article-title":"Diagnostic imaging of the equine fetlock region using radiography and ultrasonography. Part 2: The bony disorders","volume":"181","author":"Vanderperren","year":"2009","journal-title":"Vet. J."},{"key":"ref_10","first-page":"3","article-title":"Early radiographic and ultrasonographic alterations in experimental equine osteoarthritis","volume":"59","author":"Rasera","year":"2007","journal-title":"Arq. Bras. Med. Vet. Zootec."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/art.20000","article-title":"Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes","volume":"50","author":"Raynauld","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_12","first-page":"313","article-title":"Ultrasonographic examination of joints: A revolution in equine locomotor pathology","volume":"162","author":"Denoix","year":"2009","journal-title":"Bull. Acad. Vet. Fr."},{"key":"ref_13","unstructured":"Berg-Johansson, J. (2009). Biomarkers in Equine Bone and Joint Disorders. [Master\u2019s Thesis, Swedish University of Agricultural Sciences]."},{"key":"ref_14","first-page":"75","article-title":"Metabolomics: Definitions, state of the art and representative applications","volume":"41","author":"Canuto","year":"2018","journal-title":"Quim. Nova"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1021\/acs.jproteome.8b00190","article-title":"Synovial fluid metabolites differentiate between septic and nonseptic joint pathologies","volume":"17","author":"Anderson","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Laus, F., Gialletti, R., Bazzano, M., Laghi, L., Dini, F., and Marchegiani, A. (2023). Synovial fluid metabolome differentiates healthy joints from osteoarthritic joints in horses. Metabolites, 13.","DOI":"10.3390\/metabo13080913"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1038\/s41598-024-54144-3","article-title":"Comparative 1H-NMR metabolomic profiling of canine synovial fluid across four stages of osteoarthritis","volume":"14","author":"Piccionello","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-Noguera, P., Mar\u00edn, I.Z., Chavarin, B.M.G., Valderrama, M.E., L\u00f3pez-Barrera, L.D., and D\u00edaz-Torres, R. (2023). Early effects of chitosan nanoparticles with glutathione in rats with osteoarthrosis. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15082172"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2460\/ajvr.71.4.399","article-title":"Antioxidant effects of equine synovial fluid compared with hyaluronic acid and chondroitin sulfate","volume":"71","author":"Letelier","year":"2010","journal-title":"Am. J. Vet. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1294\/jes.30.13","article-title":"Oxidative stress markers in synovial fluid of thoroughbred horses with carpal bone fracture","volume":"30","author":"Tsuzuki","year":"2019","journal-title":"J. Equine Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.tvjl.2007.07.033","article-title":"The oxidant\/antioxidant equilibrium in horses","volume":"177","author":"Kirschvink","year":"2008","journal-title":"Vet. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102972","DOI":"10.1016\/j.jevs.2020.102972","article-title":"Relationship between neutrophil activity, oxidative stress, acute phase response, and lameness grade in naturally occurring acute and chronic joint disorders in horses","volume":"88","author":"Michalska","year":"2020","journal-title":"J. Equine Vet. Sci."},{"key":"ref_23","unstructured":"AAEP Horse Show Committee (1999). Guide to Veterinary Services for Horse Shows, American Association of Equine Practitioners. [7th ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.joca.2007.11.008","article-title":"Joint-dependent concentrations of bone alkaline phosphatase in serum and synovial fluid of horses with osteochondral injury: An analytical and clinical validation","volume":"16","author":"Trumble","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_25","unstructured":"McIlwraith, C.W., and Trotter, G.W. (1996). Ultrasonographic examination in diagnosis of joint disease. Joint Disease in the Horse, Saunders."},{"key":"ref_26","unstructured":"Reef, V.B. (1998). Equine Diagnostic Ultrasound, Saunders."},{"key":"ref_27","first-page":"8169172","article-title":"Osteoarthritic synovial fluid modulates cell phenotype and metabolic behavior in vitro","volume":"2019","author":"Aguiar","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1556\/avet.50.2002.2.13","article-title":"Comparative evaluation of the effect of antioxidants in the conservation of ram semen","volume":"50","year":"2002","journal-title":"Acta Vet. Hung."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation coefficients: Appropriate use and interpretation","volume":"126","author":"Schober","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.tvjl.2008.03.005","article-title":"Diagnostic imaging of the equine fetlock region using radiography and ultrasonography. Part 1: Soft tissues","volume":"181","author":"Vanderperren","year":"2009","journal-title":"Vet. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.4142\/jvs.2020.21.e21","article-title":"Synovial fluid proteomics of equine joints affected by osteoarthritis using LC-MS\/MS","volume":"21","author":"Yamada","year":"2019","journal-title":"J. Vet. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.rvsc.2020.08.001","article-title":"Allogeneic synovial membrane-derived mesenchymal stem cells do not significantly affect initial inflammatory parameters in an LPS-induced acute synovitis model","volume":"132","author":"Rosa","year":"2020","journal-title":"Res. Vet. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.jevs.2014.08.006","article-title":"Association of ultrasound and anatomopathologic findings of equine metacarpophalangeal lesions","volume":"34","author":"Bastiani","year":"2014","journal-title":"J. Equine Vet. Sci."},{"key":"ref_35","unstructured":"Cowell, R.L., and Tyler, R.D. (2002). Synovial fluid. Cytology and Hematology of the Horse, Mosby. [2nd ed.]."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Alberts, B., Johnson, A., Lewis, J., Morgan, D., Raff, M., Roberts, K., and Walter, P. (2017). Molecular Biology of the Cell, Artmed. [6th ed.].","DOI":"10.1201\/9781315735368"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Douzi, W., Guillot, X., Bon, D., Seguin, F., Boildieu, N., Wendling, D., Tordi, N., Dupuy, O., and Dugu\u00e9, B. (2020). Article1h-nmr-based analysis for exploring knee synovial fluid metabolite changes after local cryotherapy in knee arthritis patients. Metabolites, 10.","DOI":"10.3390\/metabo10110460"},{"key":"ref_38","unstructured":"Burtis, C.A., and Bruns, D.E. (2016). Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics, Elsevier. [7th ed.]."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/2\/140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:15:10Z","timestamp":1770095710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/2\/140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,31]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["vetsci13020140"],"URL":"https:\/\/doi.org\/10.3390\/vetsci13020140","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,31]]}}}