ArticleActa orthopaedica et traumatologica turcica2026
miR-655-3p is a highly accurate diagnostic biomarker for primary osteoarthritis and alleviates joint inflammation by targeting TLR4.
Article in Acta orthopaedica et traumatologica turcica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveThis 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.
methodsQuantitative 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-α, and IL-6 in the IL-1β-induced OA chondrocyte model. Enzyme-linked immunosorbent assay measured the secretion of IL-6 and TNF-α. 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.
resultsmiR-655-3p was downregulated by 44.8% in OA serum (P < .001) and 46.7% in IL-1β-induced chondrocytes (P < .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-α, IL-6, both P < .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.
conclusionmiR-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. Cite 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.
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