Effects of different 1-34 parathyroid hormone dosages on fibroblast growth factor-23 secretion in human bone marrow cells following osteogenic differentiation

The importance of fibroblast growth factor (FGF)-23 as part of a hormonal bone-kidney-axis has been well established. Lately, FGF-23 has been suggested as an independent risk factor of death in patients on chronic hemodialysis. Hyperparathyroidism is a common feature of advanced kidney failure or end-stage renal disease. The independent effect of elevated parathyroid hormone (PTH) levels on FGF-23 secretion is still a matter of debate and has not yet been studied in an in vitro model of human bone marrow cells (BMC) during osteogenic differentiation. BMC from three different donors were cultivated for 4 weeks in cell cultures devoid of vitamin D either without 1-34 PTH or with PTH concentrations of 10 or 100 pmol/L, respectively. After 28 days, protein expression of the cells was determined by immunocytochemical staining, whereas real time-polymerase chain reaction served to analyze gene expression of several osteoblastic (osteocalcin, RANKL, Runx-2 and ostase) and osteoclastic markers (RANK, TRAP-5b). The concentrations of FGF-23, ostase and TRAP-5b were determined by ELISA at weeks 2, 3 and 4. We found a basal expression of FGF-23 with no increase in FGF-23 secretion after stimulation with 10 pmol/L 1-34 PTH. Stimulation with 100 pmol/L PTH resulted in an increase in FGF-23 expression (14.1 +/- 3.6 pg/mL with no PTH, 13.7 +/- 4.0 pg/mL with 10 pmol/L, P=0.84 and 17.6 +/- 3.4 pg/mL with 100 pmol/L, P=0.047). These results suggest a vitamin D and PTH-independent FGF-23 expression in human BMC after osteogenic stimulation. As only higher PTH levels stimulated FGF-23 expression, a threshold level might be hypothesized.