Phosphate transport in osteoblasts from normal and X-linked hypophosphatemic mice.
Human hypophophatemic vitamin D-resistant rickets (X-linked hypophosphatemia-XLH) is characterized by hypophosphatemia, a decreased tubular reabsorption of phosphate (P(i)) and defective skeleton mineralization. Utilizing a mouse model (Hyp) of XLH, which demonstrates biological abnormalities and skeletal defects of XLH, we analyzed sodium-dependent phosphate transport in isolated osteoblasts derived from the calvaria of normophosphatemic and hypophosphatemic mice. Initial rates of phosphate uptake by normal and Hyp osteoblasts showed similar slopes. Osteoblasts from both normal and Hyp mice exhibited saturable, sodium-dependent phosphate transport with apparent Vmax and Km values not significantly different (normal mice, Vmax = 24.30 +/- 3.45 nmol/mg prot. 10 min, Km = 349.49 +/- 95.20 mumol/liter; Hyp mice, Vmax = 23.03 +/- 3.41 nmol/mg prot. 10 min, Km = 453.64 +/- 106.93 mumol/liter, n = 24). No differences were found in the ability of normal and Hyp osteoblasts to respond to P(i) transport after 5 hours of P(i) deprivation. Both cell types exhibited a similar increase in cAMP in response to PTH. The accumulated results demonstrate that P(i) uptake and transport in normal and Hyp mouse osteoblasts is a sodium-dependent saturable process. As osteoblast P(i) uptake and transport is apparently normal in the Hyp mouse model of XLH, the "osteoblastic failure" described for the Hyp mouse should be attributed to other mechanism(s).
Rifas
L
L
Division of Bone and Mineral Diseases, Washington University Medical Center, St. Louis, Missouri 63110.
Dawson
L L
LL
Halstead
L R
LR
Roberts
M
M
Avioli
L V
LV
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D007015:Hypophosphatemia, Familial / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000502:physiology; D014960:X Chromosome
D010281:Parathyroid Hormone; D010710:Phosphates; D012964:Sodium; D000242:Cyclic AMP