1alpha,25-dihydroxyvitamin D3 acts predominately in mature osteoblasts under conditions of high extracellular phosphate to increase fibroblast growth factor 23 production in vitro.
Osteoblasts/osteocytes are the principle sources of fibroblast growth factor 23 (FGF23), a phosphaturic hormone, but the regulation of FGF23 expression during osteoblast development remains uncertain. Because 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and inorganic phosphate (Pi) may act as potent activators of FGF23 expression, we estimated how these molecules regulate FGF23 expression during rat osteoblast development in vitro. 1,25(OH)(2)D(3)-dependent FGF23 production was restricted largely to mature cells in correlation with increased vitamin D receptor (VDR) mRNA levels, in particular, when Pi was present. Pi alone and more so in combination with 1,25(OH)(2)D(3) increased FGF23 production and VDR mRNA expression. Parathyroid hormone, stanniocalcin 1, prostaglandin E(2), FGF2, and foscarnet did not increase FGF23 mRNA expression. Thus, these results suggest that 1,25(OH)(2)D(3) may exert its largest effect on FGF23 expression/production when exposed to high levels of extracellular Pi in osteoblasts/osteocytes.
Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
Ryoko
R
Yamamoto
Tomoko
T
Minamizaki
Yuji
Y
Yoshiko
Hirotaka
H
Yoshioka
Kazuo
K
Tanne
Jane E
JE
Aubin
Norihiko
N
Maeda
D000704:Analysis of Variance; D000818:Animals; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010281:Parathyroid Hormone; D010710:Phosphates; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol