Bone as a source of FGF23: regulation by phosphate?
The identification of FGF23 as a factor involved in several disorders of phosphate regulation and of PHEX as the gene mutated in X-linked Hypophosphatemic Rickets indicates that both these genes may be involved in phosphate homeostasis, although their physiological roles are unclear. In this study, FGF23 mRNA expression was analyzed by real-time RT-PCR and found to be higher in normal human bone than in kidney, liver, thyroid, or parathyroid tissue, while expression in oncogenic osteomalacia tumor tissue was several hundred-fold higher than in bone. Expression of FGF23 mRNA in human osteoblast-like bone cells, quantitated by real-time RT-PCR, increased with increasing extracellular phosphate and was 2-fold higher in cells treated with 2 mM extracellular phosphate compared to 0 mM phosphate treatment. PHEX mRNA expression increased 1.3-fold after treatment with 2 mM phosphate. FGF23 expression in the bone cells increased with increased mineralization over a 20-day treatment period under mineralizing conditions with beta-glycerophosphate, while PHEX expression decreased. The results indicate that FGF23 mRNA expression in bone cells is regulated by extracellular phosphate and by mineralization. These results support proposals that bone may be a source of circulating FGF23 and suggest that FGF23 expression by bone is regulated.
Mirams
Michiko
M
Department of Physiology, Institute for Biomedical Research F13, University of Sydney, Sydney NSW 2006, Australia. mmirams@med.usyd.edu.au
Robinson
Bruce G
BG
Mason
Rebecca S
RS
Nelson
Anne E
AE
D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010018:Osteomalacia / Q000378:metabolism; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010710:Phosphates / Q000494:pharmacology / Q000502:physiology*; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C000717427:FGF23 protein, human; D005994:Glycerophosphates; D010710:Phosphates; D011506:Proteins; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003907:Dexamethasone; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; C031463:beta-glycerophosphoric acid