Serum microRNA signatures are indicative of skeletal fractures in post-menopausal women with and without type 2 diabetes and influence osteo-genic differentiation of mesenchymal stem cells. Homo sapiens

The objective of this study was the identification of serum microRNAs that can differentiate osteoporotic fracture patients with and without type-2 diabetes from healthy control subjects. For that purpose circulating microRNAs were profiled by real-time quantitative PCR using a custom 384-well panel in 200 µl serum samples. Univariate and multivariate statistical tools were used in order to identify single as well as combinations of circulating microRNas that were characteristic of patients with prevalent osteoporotic fractures: a qRT-PCR-based classifier consisting of miR-550a-5p, miR-96-5p, miR-32-3p and miR-486-5p can distinguish T2D women with (DMFx) and without fragility fractures (DM) with high specifitiy and sensitivity (AUC = 0.93). A classifier consisting of miR-188-3p, miR-382-3p, miR-942 and miR-155-5p was capable of differentiating between postmenopausal women with osteoporotic fractures and fracture-free controls with an AUC of 0.98. Overall design: qPCR circulating microRNA profiling. Four groups were defined: postmenopausal women without type-2 diabetes and no history of osteoporotic fractures (CO); postmenopausal women without type-2 diabetes and a history of at least one (non-recent) osteoporotic fractures (FX); postmenopausal women with type-2 diabetes and no history of osteoporotic fractures (DM); postmenopausal women with type-2 diabetes and a history of at least one (non-recent) osteoporotic fractures (DMFX)