TY - JOUR
T1 - Regulation of CYP27B1 mRNA expression in primary human osteoblasts
AU - van der Meijden, K.
AU - van Essen, H.W.
AU - Bloemers, F.W.
AU - Schulten, E.A.J.M.
AU - Bravenboer, N.
AU - Lips, P.
N1 - With supplementary material
PY - 2016/8
Y1 - 2016/8
N2 - The enzyme 1α-hydroxylase (gene CYP27B1) catalyzes the synthesis of 1,25(OH)2D in both renal and bone cells. While renal 1α-hydroxylase is tightly regulated by hormones and 1,25(OH)2D itself, the regulation of 1α-hydroxylase in bone cells is poorly understood. The aim of this study was to investigate in a primary human osteoblast culture whether parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcitonin, calcium, phosphate, or MEPE affect mRNA levels of CYP27B1. Our results show that primary human osteoblasts in the presence of high calcium concentrations increase their CYP27B1 mRNA levels by 1.3-fold. CYP27B1 mRNA levels were not affected by PTH1-34, rhFGF23, calcitonin, phosphate, and rhMEPE. Our results suggest that the regulation of bone 1α-hydroxylase is different from renal 1α-hydroxylase. High calcium concentrations in bone may result in an increased local synthesis of 1,25(OH)2D leading to an enhanced matrix mineralization. In this way, the local synthesis of 1,25(OH)2D may contribute to the stimulatory effect of calcium on matrix mineralization.
AB - The enzyme 1α-hydroxylase (gene CYP27B1) catalyzes the synthesis of 1,25(OH)2D in both renal and bone cells. While renal 1α-hydroxylase is tightly regulated by hormones and 1,25(OH)2D itself, the regulation of 1α-hydroxylase in bone cells is poorly understood. The aim of this study was to investigate in a primary human osteoblast culture whether parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcitonin, calcium, phosphate, or MEPE affect mRNA levels of CYP27B1. Our results show that primary human osteoblasts in the presence of high calcium concentrations increase their CYP27B1 mRNA levels by 1.3-fold. CYP27B1 mRNA levels were not affected by PTH1-34, rhFGF23, calcitonin, phosphate, and rhMEPE. Our results suggest that the regulation of bone 1α-hydroxylase is different from renal 1α-hydroxylase. High calcium concentrations in bone may result in an increased local synthesis of 1,25(OH)2D leading to an enhanced matrix mineralization. In this way, the local synthesis of 1,25(OH)2D may contribute to the stimulatory effect of calcium on matrix mineralization.
KW - CYP27B1
KW - Calcium
KW - Fibroblast growth factor 23
KW - Matrix extracellular phosphoglycoprotein
KW - Parathyroid hormone
KW - Primary human osteoblasts
UR - https://pure.uva.nl/ws/files/2739191/179290_Regulation_of_CYP27B1_mRNA_expression_suppl.pdf
U2 - https://doi.org/10.1007/s00223-016-0131-9
DO - https://doi.org/10.1007/s00223-016-0131-9
M3 - Article
C2 - 27016371
SN - 0171-967X
VL - 99
SP - 164
EP - 173
JO - Calcified tissue international
JF - Calcified tissue international
IS - 2
ER -