Bone as a source of FGF23: regulation by phosphate?

Bone. 2004 Nov;35(5):1192-9. doi: 10.1016/j.bone.2004.06.014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone and Bones / metabolism*
  • Calcification, Physiologic / drug effects
  • Cell Line
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Fetus / cytology
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / genetics*
  • Gene Expression / drug effects
  • Glycerophosphates / pharmacology
  • Humans
  • Kidney / chemistry
  • Kidney / metabolism
  • Liver / chemistry
  • Liver / metabolism
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteomalacia / metabolism
  • PHEX Phosphate Regulating Neutral Endopeptidase
  • Phosphates / pharmacology
  • Phosphates / physiology*
  • Proteins / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • FGF23 protein, human
  • Glycerophosphates
  • Phosphates
  • Proteins
  • RNA, Messenger
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Dexamethasone
  • PHEX Phosphate Regulating Neutral Endopeptidase
  • PHEX protein, human
  • beta-glycerophosphoric acid