Vitamin D3 Stimulates Proliferation Capacity, Expression of Pluripotency Markers, and Osteogenesis of Human Bone Marrow Mesenchymal Stromal/Stem Cells, Partly through SIRT1 Signaling

Abstract

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.

The Role of Vitamin D in the Functioning of Bone Cells

“…В експериментальних умовах у культурах МСК людини та остеобластах проведено порівняльний аналіз дії вітаміну D (холекальциферол, 25(OH)D 3 ) і його активного метаболіту (1α,25(OH) 2 D 3 ). Встановлено, що під їхньою дією експресія гена RUNX2, плюрипотентних маркерів NANOG, SOX2 і Oct4 посилюється в МСК людини, що свідчить про диференціювання цих клітин в остеогенному напрямку та відзначається накопиченням кальцію в позаклітинному матриксі [25,26]. Доведено зміну морфології МСК людини у бік остеобластичного феноти пу та підвищення продукції маркерів остеобластів -лужної фосфатази, остеопонтину та остеокальцину.…”

“…Доведено зміну морфології МСК людини у бік остеобластичного феноти пу та підвищення продукції маркерів остеобластів -лужної фосфатази, остеопонтину та остеокальцину. Також висловлено припущення, що контроль енергетичного метаболізму може бути мішенню вітаміну D у формуванні кісткової тканини та її мінералізації [26].…”

“…В ядрі остеобластів існує класичний VDR, також остеобласти експресують рецептор, локалізований на мембрані [17,26,27]. Зв'язок 1α,25(OH) 2 D 3 з VDR забезпечує пряму регуляторну дію на остеобласти, а ферменти 1α-гідроксилази (CYP27B1) і 24-гідроксилази (CYP24A1) сприяють внутрішньоклітинному перетворенню вітаміну D у 1α,25(OH) 2 D 3 і 24R,25(OH) 2 D 3 , залежно від дози.…”

Older adults and vitamin D hip fracture connections-what is the 2022 research base indicating?

“…However, it seems reasonable to suggest that some forms of hip fracture in older populations that are often not treated for possible osteoporotic risk 24 may derive some independent or collective benefit from vitamin D supplementation as far as reducing hip fracture incidence rates as well as mortality rates or further fractures post hip fracture surgery in vulnerable older adults. [24][25][26][27][28] In combination with silicon a recent basic study has revealed some degree of vitamin D influence on bone structure restoration and improved calcium absorption that appears to offer a possible avenue for enhancing bone related regeneration and that may prove valuable to examine further in the realm of hip fracture prevention and that is supported by human clinical evidence, [29][30][31][32] even though its presence may not impact number of falls or injurious falls that often lead to hip fractures. 33 However, there are multiple contrary study findings as well as multiple design problems that remain in this body of research, even though more favorable potentially relevant clinical findings prevail than not.…”

Eldecalcitol prevented OVX-induced osteoporosis through inhibiting BMSCs senescence by regulating the SIRT1-Nrf2 signal

“…Studies have examined the relationship between vitamin D with SIRT1 and Nrf2. Vitamin D increases the osteogenic potential of BMSCs by raising SIRT1 (Borojević et al, 2022). Vitamin D is also found to regulate Nrf2 to inhibit oxidative stress and DNA damage in order to play a role in delaying senescence .…”