MiR-370-3p regulate TLR4/SLC7A11/GPX4 to alleviate the progression of glucocorticoids-induced osteonecrosis of the femoral head by promoting osteogenesis and suppressing ferroptosis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objectives Osteonecrosis of the femoral head (ONFH) represents a severe complication of glucocorticoids (GCs) therapy in clinical settings. MicroRNAs (miRNAs) are critically involved in the progression of GCs-induced ONFH, with ferroptosis playing a central role in its pathology. However, the regulatory effects of specific miRNAs targeting ferroptosis in ONFH have not been previously explored. The aim of this study was to elucidate the effect and the specific molecular mechanisms of miR-370-3p in the progression of GCs-induced ONFH. Methods In this study, we first established a rat model of GCs-induced ONFH and analyzed changes in osteogenesis and ferroptosis. Subsequently, we performed miRNA sequencing on bone marrow-derived mesenchymal stem cells (BMSCs) after dexamethasone treatment. In vitro, we assessed the effects of miR-370-3p on cell proliferation, osteogenic activities, and ferroptosis in BMSCs. We used dual luciferase assays to identify the target gene of miR-370-3p, examining its regulatory effects on osteogenesis and ferroptosis. In vivo, we estimated the effect of miR-370-3p on the femoral head by isolating exosomes from BMSCs overexpressing miR-370-3p and administering them to rats. Results We observed that impaired osteogenesis and enhanced ferroptosis are principal pathogenic factors in the progression of GCs-induced ONFH. We identified miR-370-3p as a significa

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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