Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells.
Fibroblast growth factor-23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate (Pi) as well as 1,25-dihydroxyvitamin D(3). Recent studies also suggest a correlation between serum levels of FGF23 and parathyroid hormone (PTH) in patients with chronic kidney disease. It is, however, unknown whether FGF23 directly modulates PTH expression, or whether the correlation is secondary to abnormalities in Pi and vitamin D metabolism. The objective of the current study was therefore to elucidate possible direct effects of FGF23 on bovine parathyroid cells in vitro. Treatment of parathyroid cells with a stabilized form of recombinant FGF23 (FGF23(R176Q)) induced a rise in early response gene-1 mRNA transcripts, a marker of FGF23 signaling. FGF23(R176Q) potently and dose-dependently decreased the PTH mRNA level within 12 h. In agreement, FGF23(R176Q) also decreased PTH secretion into conditioned media. In contrast, FGF23(R176Q) dose-dependently increased 1alpha-hydroxylase expression within 3 h. FGF23 (R176Q) did not affect cell viability nor induce apoptosis, whereas a small but significant increase in cell proliferation was found. We conclude that FGF23 is a negative regulator of PTH mRNA expression and secretion in vitro. Our data suggest that FGF23 may be a physiologically relevant regulator of PTH. This defines a novel function of FGF23 in addition to the previously established roles in controlling vitamin D and Pi metabolism.
Krajisnik
Tijana
T
Department of Medical Sciences, Uppsala University Hospital, Sweden.
Björklund
Peyman
P
Marsell
Richard
R
Ljunggren
Osten
O
Akerström
Göran
G
Jonsson
Kenneth B
KB
Westin
Gunnar
G
Larsson
Tobias E
TE
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002417:Cattle; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003864:Depression, Chemical; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005434:Flow Cytometry; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase