Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

Osteoporotic fractures (OF) are the main consequence of osteoporosis. Bone mineral density (BMD)‑based diagnosis lacks sensitivity for early osteopoenia (OP) and OF risk. This study evaluated serum miR‑642a‑3p as a diagnostic marker for OP and OF and investigated its mechanism in osteoclast differentiation via IFNG. Bioinformatic analysis of GSE74209 was performed. Serum miR‑642a‑3p levels were measured by RT‑qPCR in 30 healthy controls (HCs), 40 OP patients and 40 OF patients. Diagnostic performance, correlation with clinical indicators, and risk prediction for OF were analysed using logistic regression. A dual‑luciferase reporter assay confirmed miR‑642a‑3p targeting IFNG. RT‑qPCR and Western blot assessed downstream osteoclast markers and the effect of TNF‑α‑induced inflammation on miR‑642a‑3p. Serum miR‑642a‑3p was found significantly higher in OP and OF groups than in HCs. The AUC for distinguishing HCs from OP patients was 0.834. miR‑642a‑3p negatively correlated with 25(OH)D and was identified as an independent risk factor for OP. The reporter assay confirmed direct targeting of IFNG by miR‑642a‑3p. Disruption of this axis altered expression of osteoclast markers (NFATc1, CTSK, c‑FOS). In the TNF‑α‑induced inflammatory model, miR‑642a‑3p increased, IFN-γ decreased, and osteoclast markers were up-regulated, indicating that miR‑642a‑3p promotes osteoclast differentiation through IFNG suppression. We conclude that the serum miR-642a-3p is a diagnostic biomarker for OP and OF. It promotes osteoclast differentiation by targeting and inhibiting IFNG, identifying a new miR-642a-3p/IFNG regulatory axis in OP.

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