Clinical significance of serum miR-328-3p for fracture risk prediction in osteoporosis and its regulatory function in iron accumulation-induced osteoblast injury by targeting TSC1.

Fracture is a common adverse outcome of osteoporosis involving osteoblast injury. The significance of miR-328-3p was evaluated to explore a novel biomarker and to provide a theoretical reference for disease management. This study enrolled 109 patients diagnosed with osteoporosis and 82 healthy individuals with matched clinical features as controls. Serum miR-328-3p was analyzed in both groups by Polymerase Chain Reaction. The clinical significance of miR-328-3p was estimated from the perspectives of early screening, severity correlation, and fracture prediction. In vitro, an iron-accumulation cell model was established by the treatment of ferric ammonium citrate in osteoblasts. The regulatory effects of miR-328-3p were evaluated based on the level of oxidative stress, ferroptosis, cell viability, and osteogenic differentiation. Significant downregulation of miR-328-3p was observed in osteoporosis patients relative to healthy individuals, which showed discriminating ability. Serum miR-328-3p in osteoporosis patients was positively correlated with the bone mineral density (BMD) of patients and negatively correlated with the ferritin levels. miR-328-3p served as a risk factor predicting the occurrence of fractures in osteoporosis patients. In osteoblasts, iron accumulation induced oxidative stress and ferroptosis, suppressed cell proliferation, and osteogenic differentiation. Overexpressing miR-328-3p alleviated iron accumulation-induced cell injury, and Tuberous Sclerosis Complex 1 (TSC1) was revealed to mediate the function of miR-328-3p. Reduced serum miR-328-3p served as a biomarker for screening osteoporosis and predicting fracture risk. Overexpressing miR-328-3p mediates iron accumulation-induced osteoblast injury by targeting TSC1.