TY - JOUR A1 - Borojević, Ana A1 - Jauković, Aleksandra A1 - Kukolj, Tamara A1 - Mojsilović, Slavko A1 - Obradović, Hristina A1 - Trivanović, Drenka A1 - Živanović, Milena A1 - Zečević, Željko A1 - Simić, Marija A1 - Gobeljić, Borko A1 - Vujić, Dragana A1 - Bugarski, Diana T1 - Vitamin D3 stimulates proliferation capacity, expression of pluripotency markers, and osteogenesis of human bone marrow mesenchymal stromal/stem cells, partly through SIRT1 signaling JF - Biomolecules N2 - The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine — mainly in combination with various biomaterial matrices — has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MSCs, while it reduced their senescence. Moreover, increased sirtuin 1 (SIRT1) expression was detected upon treatment with VD3, which mediated VD3-promoted osteogenesis and, partially, the stemness features through NANOG and SOX2 upregulation. In contrast, the effects of VD3 on proliferation, Oct4 expression, and senescence were SIRT1-independent. Altogether, these data indicate that VD3 has strong potential to modulate BM-MSCs' features, partially through SIRT1 signaling, although the precise mechanisms merit further investigation. KW - bone marrow mesenchymal stromal cells (BM-MSCs) KW - vitamin D3 (cholecalciferol, VD3) KW - SIRT1 KW - regenerative potential KW - stemness KW - osteogenesis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262203 SN - 2218-273X VL - 12 IS - 2 ER -