AJP - Endocrinology and Metabolism, Vol 266, Issue 1 E33-E38, Copyright © 1994 by American Physiological Society
Phosphate transport by osteoblasts from X-linked hypophosphatemic mice
B. Ecarot, J. Caverzasio, M. Desbarats, J. P. Bonjour and F. H. Glorieux
Shriners Hospital, Department of Surgery, Montreal, Quebec, Canada.
Hypophosphatemic vitamin D-resistant rickets is characterized by impaired
renal reabsorption of Pi. The underlying mechanism of this abnormality
remains unknown. Because the osteoblast is likely a target for the HYP
mutation, we investigated the Pi transport activity in osteoblasts isolated
from the murine homologue for the human disease, the Hyp mouse. Kinetic
analysis of sodium-dependent Pi uptake in quiescent normal and Hyp
osteoblasts indicated no significant differences in apparent maximal
capacity (Vmax) and apparent affinity (Km) of the carrier for Pi. In
rapidly growing cells, higher levels of Pi uptake were observed in mutants
cells associated with a 1.4- to 1.7-fold increase in Vmax and no change in
Km for Pi. This increase in Pi uptake seemed related to changes in the
sodium electrochemical gradient inasmuch as a similar increase was observed
in alanine uptake. The adaptive response of sodium-dependent Pi transport
to Pi deprivation was not altered in mutant cells relative to normal cells.
To test whether the expression of a Pi transport defect was dependent on a
humoral factor for its expression, we evaluated the activity of the serum
from Hyp mice on Pi transport in osteoblasts from both genotypes. No
difference in activity was observed between sera from normal and mutant
mice. In summary, cultured osteoblasts derived from Hyp mice did not
express impaired sodium-dependent Pi transport when compared with cells
from normal mice.
