Circulating miR-107 as a diagnostic biomarker of osteoporotic vertebral compression fracture increases bone formation in vitro and in vivo

Abstract

AimsThis study aimed to examine the key circulating microRNAs (miRNAs) in the plasma of patients with osteoporotic vertebral compression fracture and assess their potential role as diagnostic biomarkers and explore their function in vitro and in vivo. MethodsWeighted gene co-expression network analysis (WGCNA) was applied to identify hub miRNAs for subsequent analysis. The candidate miRNAs were tested using plasma from 144 patients and the results were applied to construct receiver operating characteristic (ROC) curves to assess their diagnostic value. In addition, the function of the target miRNA was validated in MC3T3-E1 cells, human bone marrow-derived mesenchymal stromal cells (BMSCs), and an ovariectomized (OVX) mouse model. Key findingsSeven modules were obtained by WGCNA analysis. The expression levels of circulating miR-107 in the red module were significantly lower in osteoporotic patients than in healthy controls. In addition, miR-107 provided discrimination with an AUC > 85 % by ROC analyses to differentiate women osteoporosis patients from healthy controls and differentiate women osteoporotic patients with vertebral compression fractures from osteoporotic patients without vertebral compression fractures. In vitro experiments revealed that miR-107 levels were increased in osteogenically induced MC3T3-E1 cells and BMSCs and transfection with synthetic miR-107 could promote bone formation. Lastly, the bone parameters were improved by miR-107 upregulation in OVX mice. SignificanceOur findings show that circulating miR-107 plays an essential role in facilitating osteogenesis and may be a useful diagnostic biomarker and therapeutic target in osteoporosis.