EFFECT OF 1,25-DIHYDROXYVITAMIN D-3 TREATMENT ON BONE-FORMATION BY TRANSPLANTED CELLS FROM NORMAL AND X-LINKED HYPOPHOSPHATEMIC MICE

Bone cells isolated from the Hyp mouse, the murine homologue for hypop hosphatemic vitamin D-resistant rickets, produce abnormal bone when tr ansplanted to either normal or phosphate-supplemented Hyp mice, To ass ess whether correction of the bone formation by mutant cells transplan ted into either normal or Hyp mice could be achieved in the presence o f supraphysiologic serum concentrations of 1,25-dihydroxyvitamin D-3 ( 1,25-(OH)(2)D-3), recipient mice of both genotypes were infused contin uously with 1,25-(OH)(2)D-3 (0.2 mu g/kg/day). Bone nodules present in transplants recovered after 14 days were characterized by measuring t he osteoid thickness and volume, Administration of 1,25-(OH)(2)D-3 to Hyp mice corrected the defective bone formation by normal cells but no t by pair-transplanted Hyp cells, despite normalization of serum phosp hate levels and 3-fold increases in serum 1,25-(OH)(2)D-3, The osteoid thickness and volume in Hyp transplants into 1,25-(OH)(2)D-3-treated Hyp mice were, however, markedly reduced down to values observed for H yp transplants into recipient normal mice, Administration of 1,25-(OH) (2)D-3 to normal mice improved further bone formation by mutant cells without affecting that by pair-transplanted normal cells, Administrati on of 24,25-(OH)(2)D-3 (1 mu g/kg/day) combined with 1,25-(OH)(2)D-3 t o recipient mice of both genotypes prevented the sharp fall in serum 2 4,25-(OH)(2)D-3 but was not more beneficial than 1,25-(OH)(2)D-3 alone for improving bone formation by transplanted Hyp cells, These observa tions demonstrate an abnormal response of the mutant cells to the extr acellular environment and support the concept of an intrinsic osteobla st defect in the Hyp mouse.