PHOSPHATE-TRANSPORT BY OSTEOBLASTS FROM X-LINKED HYPOPHOSPHATEMIC MICE

Hypophosphatemic vitamin D-resistant rickets is characterized by impaired renal reabsorption of P-i, The underlying mechanism of this abnormality remains unknown. Because the osteoblast is likely a target for the HYP mutation, we investigated the P-i transport activity in osteoblasts isolated from the murine homologue for the human disease, the Hyp mouse. Kinetic analysis of sodium-dependent P-i uptake in quiescent normal and Hyp osteoblasts indicated no significant differences in apparent maximal capacity (V-max) and apparent affinity (K-m) of the carrier for P-i. In rapidly growing cells, higher levels of P-i uptake were observed in mutants cells associated with a 1.4- to 1.7-fold increase in V-max and no change in K-m for P-i. This increase in P-i 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 P-i transport to P-i deprivation was not altered in mutant cells relative to normal cells. To test whether the expression of a P-i transport defect was dependent on a humoral factor for its expression, we evaluated the activity of the serum from Hyp mice on P-i 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 P-i transport when compared with cells from normal mice.