PHOSPHATE-TRANSPORT BY OSTEOBLASTS FROM X-LINKED HYPOPHOSPHATEMIC MICE

Hypophosphatemic vitamin D-resistant rickets is characterized by impai red renal reabsorption of P-i, The underlying mechanism of this abnorm ality remains unknown. Because the osteoblast is likely a target for t he HYP mutation, we investigated the P-i transport activity in osteobl asts isolated from the murine homologue for the human disease, the Hyp mouse. Kinetic analysis of sodium-dependent P-i uptake in quiescent n ormal and Hyp osteoblasts indicated no significant differences in appa rent maximal capacity (V-max) and apparent affinity (K-m) of the carri er 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 se emed related to changes in the sodium electrochemical gradient inasmuc h as a similar increase was observed in alanine uptake. The adaptive r esponse of sodium-dependent P-i transport to P-i deprivation was not a ltered in mutant cells relative to normal cells. To test whether the e xpression of a P-i transport defect was dependent on a humoral factor for its expression, we evaluated the activity of the serum from Hyp mi ce 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 im paired sodium-dependent P-i transport when compared with cells from no rmal mice.