{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:04:42Z","timestamp":1789643082255,"version":"4.0.0"},"reference-count":0,"publisher":"AVES YAYINCILIK A.\u015e.","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["AOTT"],"abstract":"<jats:p>Objective: This study aimed to evaluate the potential of miR-655-3p as a diagnostic biomarker for primary osteoarthritis (OA) and to investigate its intrinsic molecular mechanisms as a means of addressing the lack of sensitive early diagnostic biomarkers and targeted anti-inflammatory therapies for this prevalent degenerative joint disorder.\r\nMethods: Quantitative real-time polymerase chain reaction was performed to measure (1) miR-655-3p levels in the serum of 93 primary OA patients and 60 non-OA controls, (2) miR-655-3p levels in the synovial fluid of OA patients, and (3) messenger RNA (mRNA) expression of TLR4, RelA, TNF-\u03b1, and IL-6 in the IL-1\u03b2\u2013induced OA chondrocyte model. Enzyme-linked immunosorbent assay measured the secretion of IL-6 and TNF-\u03b1. Receiver operating characteristic curve (ROC) analysis assessed its diagnostic value in multiple clinical scenarios. Cell function assays investigated cell viability and apoptosis. Target genes were predicted via 3 databases, and the interaction between miR-655-3p and TLR4 was verified by dual-luciferase reporter assay and Western blot. Rescue experiments were performed to confirm the mechanistic specificity.\r\nResults: miR-655-3p was downregulated by 44.8% in OA serum (P &lt; .001) and 46.7% in IL-1\u03b2\u2013induced chondrocytes (P &lt; .001). ROC curve analysis showed an overall area under the curve (AUC) of 0.9518 (95% CI: 0.920-0.983), with consistent high accuracy in distinguishing OA from healthy controls (AUC = 0.9509), meniscus injury patients (AUC = 0.9425), and mild OA from controls (AUC = 0.9306). Serum miR- 655-3p levels were negatively correlated with OA severity (American Academy of Orthopaedic Surgeons score, P = .010) and inflammatory factor levels (TNF-\u03b1, IL-6, both P &lt; .001). Dual-luciferase assay confirmed TLR4 as a direct target of miR-655-3p; miR 655-3p overexpression reduced TLR4 protein expression by 48.7%, while inhibition increased it by 52.8%. TLR4 overexpression completely reversed the antiinflammatory and anti-apoptotic effects of miR-655-3p in OA chondrocytes.\r\nConclusion: miR-655-3p is a highly accurate diagnostic biomarker for primary OA, and upregulating miR-655-3p may provide a novel clinical treatment direction by targeting TLR4 to alleviate joint inflammation.\r\n\u00a0\r\nCite this article as: Li R, Chen C, Chen D. MiR-655-3p is a highly accurate diagnostic biomarker for primary osteoarthritis and alleviates joint inflammation by targeting TLR4. Acta Orthop Traumatol Turc., 2026; 60(4), 0803, doi: 10.5152\/j.aott.2026.25803.<\/jats:p>","DOI":"10.5152\/j.aott.2026.25803","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:55:29Z","timestamp":1789642529000},"source":"Crossref","is-referenced-by-count":0,"title":["miR-655-3p is a highly accurate diagnostic biomarker for primary osteoarthritis and alleviates joint inflammation by targeting TLR4"],"prefix":"10.5152","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5570-4383","authenticated-orcid":false,"given":"Ruye","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1949-5798","authenticated-orcid":false,"given":"Chao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1024-1100","authenticated-orcid":false,"given":"Deming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3111","published-online":{"date-parts":[[2026,8,21]]},"container-title":["Acta Orthopaedica et Traumatologica Turcica"],"original-title":[],"link":[{"URL":"https:\/\/www.aott.org.tr\/index.php\/pub\/article\/download\/4207\/4138","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.aott.org.tr\/index.php\/pub\/article\/download\/4207\/4138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:55:29Z","timestamp":1789642529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aott.org.tr\/index.php\/pub\/article\/view\/4207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,7,9]]}},"URL":"https:\/\/doi.org\/10.5152\/j.aott.2026.25803","relation":{},"ISSN":["2589-1294","1017-995X"],"issn-type":[{"value":"2589-1294","type":"electronic"},{"value":"1017-995X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}