Raw data set for: Fleischhacker V, Milosic F,  Bricelj M, Kührer K, Wahl-Figlash K, Heimel P, Diendorfer A, Nardini E, Fischer I, Stangl H, Pietschmann P, Hackl M, Foisner R, Grillari J, Hengstschläger M, and Osmanagic-Myers S. Aged-vascular niche hinders osteogenesis of mesenchymal stem cells through paracrine repression of Wnt-axis. Aging Cell. 2024 Jun;23(6):e14139. doi: 10.1111/acel.14139.  Epub 2024 Apr 5.

Age-induced decline in osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) potentiates osteoporosis and increases risk for bone fractures. Despite epidemiology studies reporting concurrent development of vascular- and bone diseases in the elderly, the underlying mechanisms for the vascular-bone cross-talk in aging are largely unknown. In this study, we show that accelerated endothelial aging deteriorates bone tissue through paracrine repression of Wnt-driven-axis in BMSCs. Here, we utilize physiologically aged mice in conjunction with our transgenic endothelial progeria mouse model (Hutchinson-Gilford progeria syndrome; HGPS) that displays hallmarks of an aged bone marrow vascular niche. We find bone defects associated with diminished BMSC osteogenic differentiation that implicate the existence of angiocrine factors with long-term inhibitory effects. microRNA-transcriptomics of HGPS-patient plasma combined with aged-vascular niche analyses in progeria mice reveal abundant secretion of Wnt-repressive microRNA-31-5p. Moreover, we show that inhibition of microRNA-31-5p as well as selective Wnt-activator CHIR99021 boost the osteogenic potential of BMSCs through de-repression and activation of the Wnt-signalling, respectively. Our results demonstrate that the vascular niche significantly contributes to osteogenesis defects in aging and pave ground for microRNA-based therapies of bone loss in elderly.