{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:05:44Z","timestamp":1793408744349,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Temporomandibular disorders (TMDs) encompass a broad spectrum of functional and structural abnormalities of the temporomandibular joint (TMJ). Conventional diagnostic tools, although essential, often fail to capture the underlying biochemical mechanisms driving disease progression. Synovial fluid (SF), by virtue of its direct proximity to intra-articular tissues, represents an accessible biological matrix for identifying molecular signatures of inflammation, cartilage degradation, lubrication failure, oxidative stress, and angiogenic activation. The objective of this review is to synthesize current evidence on SF proteomics in TMD and evaluate its potential translational value in precision medicine. Materials and Methods: A narrative review of the literature was conducted on PubMed to identify human studies focused on SF proteomic and biochemical biomarkers in TMD. Eligible studies included original research articles assessing SF composition in relation to specific TMJ pathologies, diagnostic categories, or clinical phenotypes. Extracted data included study design, sample characteristics, analytic methodology, biomarkers investigated, and key findings. Google Gemini (Google LLC, Mountain View, CA, USA) was used as an AI-assisted tool to support language editing and manuscript writing during the preparation of this article. The use of this tool was limited to linguistic refinement; all scientific content, data interpretation, and conclusions were formulated and verified by the authors. Results: Across the analyzed studies, TMD phenotypes\u2014particularly disc displacement with or without reduction (DDwR, DDwoR) and osteoarthritis (OA)\u2014were characterized by consistent alterations in cytokines (IL-1\u03b2, IL-6, IL-8, TNF-\u03b1), extracellular matrix (ECM) components (aggrecan, glycosaminoglycans (GAGs), decorin, MMP-2, MMP-9), lubrication molecules (lubricin\/PRG4), oxidative stress mediators (myeloperoxidase (MPO), nitric oxide (NO), glutathione peroxidase (GPX)), adipokines (chemerin, resistin, adiponectin), and angiogenic factors (vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2)). Recent liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) analyses further revealed phenotype-specific protein clusters and pathways related to inflammation, ferroptosis, hypoxia signaling, and proteoglycan metabolism. Conclusions: Current evidence suggests that SF proteomics and multi-analyte biomarker profiling offer a promising, hypothesis-generating approach for understanding the biological mechanisms underlying TMD. The integration of proteomic, metabolic, and inflammatory markers holds future potential for diagnostic panel development; however, prospective clinical validation is still required before SF-based molecular profiling can be implemented as a precision medicine tool in TMJ disorders.<\/jats:p>","DOI":"10.3390\/medicina62061179","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:11:22Z","timestamp":1781709082000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Precision Medicine in Temporomandibular Joint Disorders: A Synovial Fluid Biomarker-Based Literature Review"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1293-2107","authenticated-orcid":false,"given":"Francesco","family":"Maff\u00eca","sequence":"first","affiliation":[{"name":"Instituto Portugu\u00eas da Face, 1500-493 Lisbon, Portugal"},{"name":"Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-8090","authenticated-orcid":false,"given":"Francisco","family":"Salvado","sequence":"additional","affiliation":[{"name":"Clinica Universit\u00e1ria de Estomatologia, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHUNL), 1349-019 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3326-4825","authenticated-orcid":false,"given":"Paola","family":"Bonavolont\u00e0","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-2875","authenticated-orcid":false,"given":"Henrique Jos\u00e9","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas da Face, 1500-493 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sanz","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas da Face, 1500-493 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-0328","authenticated-orcid":false,"given":"Stefania","family":"Troise","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca Renato","family":"De Fazio","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6479-6130","authenticated-orcid":false,"given":"Giovanni","family":"Dell\u2019Aversana Orabona","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Faustino","family":"\u00c2ngelo","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas da Face, 1500-493 Lisbon, Portugal"},{"name":"Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Clinica Universit\u00e1ria de Estomatologia, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHUNL), 1349-019 Lisbon, Portugal"},{"name":"Servi\u00e7o de Estomatologia, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, 1349-019 Lisbon, Portugal"},{"name":"Centre for Rapid and Sustainable Product Development, Polytechnic Institute of Leiria, 2430-028 Leiria, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.11607\/jop.1151","article-title":"Diagnostic criteria for temporomandibular disorders (DC\/TMD) for clinical and research applications: Recommendations of the International RDC\/TMD Consortium Network and Orofacial Pain Special Interest Group","volume":"28","author":"Schiffman","year":"2014","journal-title":"J. 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