Vitamin D3 Stimulates Proliferation Capacity, Expression of Pluripotency Markers, and Osteogenesis of Human Bone Marrow Mesenchymal Stromal/Stem Cells, Partly through SIRT1 Signaling
Ana Borojević,
Aleksandra Jauković,
Tamara Kukolj,
Slavko Mojsilović,
Hristina Obradović,
Drenka Trivanović,
Milena Živanović,
Željko Zečević,
Marija Simić,
Borko Gobeljić,
Dragana Vujić,
Diana Bugarski
Affiliations
Ana Borojević
Mother and Child Health Care Institute of Serbia ‘’Dr Vukan Čupić’’, 11000 Belgrade, Serbia
Aleksandra Jauković
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Tamara Kukolj
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Slavko Mojsilović
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Hristina Obradović
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Drenka Trivanović
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Milena Živanović
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Željko Zečević
Mother and Child Health Care Institute of Serbia ‘’Dr Vukan Čupić’’, 11000 Belgrade, Serbia
Marija Simić
Mother and Child Health Care Institute of Serbia ‘’Dr Vukan Čupić’’, 11000 Belgrade, Serbia
Borko Gobeljić
Mother and Child Health Care Institute of Serbia ‘’Dr Vukan Čupić’’, 11000 Belgrade, Serbia
Dragana Vujić
Mother and Child Health Care Institute of Serbia ‘’Dr Vukan Čupić’’, 11000 Belgrade, Serbia
Diana Bugarski
Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
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.
