Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro.

摘要: Standard DXA measurements, including Fracture Risk Assessment Tool (FRAX) scores, have shown limitations in assessing fracture risk Type 2 Diabetes (T2D), underscoring the need for novel biomarkers and suggesting that other pathomechanisms may drive diabetic bone fragility. MicroRNAs (miRNAs) are secreted into circulation from cells of various tissues proportional to local disease severity were recently found be crucial homeostasis T2D. Here, we studied, if which circulating miRNAs or combinations can discriminate best status a well-characterized study postmenopausal osteoporosis (n = 80 women). We then tested most discriminative frequent vitro. Using miRNA-qPCR-arrays, showed 48 differentiate T2D women several four diabetes-related fractures with high specificity sensitivity (area under receiver-operating characteristic curve values [AUCs], 0.92 0.96; 95% CI, 0.88 0.98). For osteoporotic arm, 23 fracture-indicative potential AUCs 0.97 1.00 (95% 0.93 1.00). Because role those present among all miRNA had not been described, performed vitro functional studies human adipose tissue-derived mesenchymal stem investigate effect miR-550a-5p, miR-188-3p, miR-382-3p on osteogenesis, adipogenesis, cell proliferation. significantly enhanced osteogenic differentiation (p < 0.001), whereas miR-550a-5p inhibited this process (p < 0.001). Both miRNAs, impaired adipogenic differentiation, miR-188-3p did exert an adipogenesis. None affected Our data suggest first time linked fragility should further investigated their diagnostic detailed function bone. © 2016 American Society Bone Mineral Research.