Hypophosphatemic rickets accompanying McCune-Albright syndrome: evidence that a humoral factor causes hypophosphatemia.

摘要

McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine.