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.
The 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 are decreases 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.
Abbreviations:
1α,25(OH)2D (1α,25-dihydroxyvitamin D), 25(OH)D (25-hydroxyvitamin D), ALP (alkaline phosphatase activity), CFU-F (colony-forming unit-fibroblasts), eGFR (estimated glomerular filtration rate), FACS (fluorescence activated cell sorting), FBS-HI (heat-inactivated fetal bovine serum), hMSCs (human marrow stromal cells), IGF-I (insulin-like growth factor-I), PBMCs (peripheral blood monocytes), PTH (parathyroid hormone), PTHR1 (PTH/PTHrP receptor), VDR (vitamin D receptor)Keywords
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Article info
Publication history
Published online: February 01, 2013
Accepted:
January 5,
2013
Received:
August 6,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
