Vitamin D metabolism in human bone marrow stromal (mesenchymal stem) cells

Abstract

There are many human extra-renal tissues and cells that biosynthesize 1α,25-dihydroxyvitamin D (1α,25(OH)2D) by the action of CYP27B1/1α-hydroxylase. Human marrow stromal cells (hMSCs), also known as mesenchymal stem cells, were isolated from marrow discarded from well-characterized, consented subjects during common orthopedic procedures. Human MSCs can give rise to osteoblasts, chondrocytes, adipocytes, and other lineages. Their in vitro differentiation to osteoblasts is stimulated by 1α,25(OH)2D, and recent evidence indicates that they have the capacity to metabolize vitamin D in a regulated manner. Human MSCs express the vitamin D receptor, 25-hydroxylases, 1α-hydroxylase, and 24-hydroxylase; stimulation of in vitro osteoblastogenesis by 25(OH)D depends on the activity of CYP27B1/1α-hydroxylase. Finding that hMSCs are a both a producer and target of 1α,25(OH)2D suggests a potential autocrine/paracrine role of vitamin D metabolism in osteoblast differentiation. Expression and enzyme activity of CYP27B1/1α-hydroxylase are upregulated by substrate 25(OH)D and Parathyroid Hormone (PTH) and are downregulated by 1α,25(OH)2D. With subject age, there is a decrease in basal osteoblast potential and in stimulation of osteoblastogenesis by 1α,25(OH)2D, 25(OH)D, and PTH. In vitro treatment with a combination of 25(OH)D and PTH rejuvenated osteoblastogenesis with hMSCs from elders; this was attributable to increases in CYP27B1/1α-hydroxylase and in receptor for each hormone by the reciprocal factor. Other clinical variables beside age, i.e. low serum 25(OH)D or low estimated glomerular filtration rate, are correlated with reduced osteoblastogenesis. These studies suggest that osteoblastogenesis may not be optimal unless there is sufficient serum 25(OH)D substrate for hMSCs to synthesize and respond to local 1α,25(OH)2D.

Incorporation of nanohydroxyapatite and vitamin D3 into electrospun PCL/Gelatin scaffolds: The influence on the physical and chemical properties and cell behavior for bone tissue engineering

“…Moreover, cell proliferation was observed to be greater on PCL/Gel/nHA/Vit D3 scaffold than on PCL/Gel/nHA scaffold. The results of the fluorescent stain with DAPI proved that MG‐63 cells had higher proliferation on PCL/Gel/nHA/Vit D3 nanocomposite scaffold as was confirmed by the results of the previous research mentioned in this study …”

“…The increased ALP activity observed on PCL/Gel/nHA/Vit D3 scaffold could be due to (1) the synergistic effect of gelatin, which increases the adhesion and proliferation of osteoblastcells on the scaffold, (2) nHA, which has a crystalline structure similar to bone mineral phase and is considered as “gold‐standard” for osteoconductive scaffolds, and (3) Vit D3, which has direct impact on increased ALP activity due to increased calcium deposits production and thus, increased matrix mineral level. The results ultimately helped to emerge differentiation for osteoblasts and obtain a mineral matrix with PCL/Gel/nHA/Vit D3 combination for application in bone tissue engineering under in vitro conditions …”

Chronic kidney disease and vitamin D metabolism in human bone marrow–derived MSCs

“…Bone, kidney, and intestine are considered classic target tissues of 1α,25(OH) 2 D, and those organ systems interact to regulate mineral homeostasis, but data now indicate that all cells may be targets of 1α,25(OH) 2 D action . Genomic actions of 1α,25(OH) 2 D entail its direct binding to a heterodimer of the nuclear vitamin D receptor (VDR) and RXR receptor complex, with subsequent binding to specific DNA sequences, the vitamin D response elements.…”

Effects of magnesium degradation products on mesenchymal stem cell fate and osteoblastogenesis

“…However, these effects are [37]. In addition to its role in calcium homeostasis, VDR and its high affinity ligand (1α,25(OH)2D3 -vitamin D3) also stimulate osteoblastogenesis in MSCs in a potential autocrine/paracrine manner [38]. In this study, Mg extracts with and without osteoblastic factors influenced VDR signalling member expressions.…”