ArticleJournal of orthopaedic surgery and research2025
The diagnostic and therapeutic potential of miR-3149 in osteoporotic fractures through SMAD4.
Article in Journal of orthopaedic surgery and research, 2025. 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
backgroundOsteoporotic fractures (OPF) are one of the most common bone diseases in aging societies. MiR-3149 is a short non-coding RNA, its expression level, therapeutic effects, and mechanisms in OPF remain unclear. PURPOSE: This study aims to explore the impact of miR-3149 on OPF progression and uncover its mechanism for influencing OPF progression via SMAD4.
methodsIn this study, we first used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect miR-3149 expression levels in the serum of OPF patients. Then, we assessed miR-3149's diagnostic value for OPF via ROC curve analysis. Using cell counting kit-8 (CCK-8) assays, flow cytometry, and RT-qPCR, we explored miR-3149's effects on cell proliferation, apoptosis, and the expression of key factors RANK and NFATc1. Furthermore, we examined SMAD4 expression in RAW264.7 cells and conducted a dual-luciferase reporter assay to confirm the interaction between miR-3149 and SMAD4. Finally, we analyzed how miR-3149 regulates SMAD4 expression and investigated the effects of miR-3149-mediated SMAD4 regulation on cell function.
resultsThis study reveals that miR-3149 is markedly upregulated in the OPF group, effectively differentiating the control and case groups. MiR-3149 knockdown suppressed RAW264.7 cell proliferation and osteoclastic differentiation, while inducing apoptosis. Notably, SMAD4, a downstream target gene of miR-3149, was low-expressed in RANKL-induced RAW264.7 cells, and exhibits specific binding with miR-3149. Co-transfection with pcDNA-SMAD4 reversed the effects of mimic-miR on RAW264.7 cell proliferation, apoptosis, and osteoclastic induction.
conclusionsDown-regulating miR-3149 inhibited the osteoclastic generation ability of RAW264.7 by up-regulating SMAD4 expression.
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