Am J Physiol Cell Physiol AJP: Endocrinology and Metabolism
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Am J Physiol Cell Physiol 283: C1414-C1421, 2002. First published August 14, 2002; doi:10.1152/ajpcell.00135.2002
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Vol. 283, Issue 5, C1414-C1421, November 2002

Role of abnormal neutral endopeptidase-like activities in Hyp mouse bone cells in renal phosphate transport

Stéphanie G. Dubois1, Andréa Frota Ruchon2, Aline Delalandre1, Guy Boileau2, and Daniel Lajeunesse1

1 Unité de recherche en Arthrose, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Montreal H2L 4M1; and 2 Département de Biochimie, Université de Montréal, Montreal, Quebec, Canada H3C 3J7

We investigated whether the absence of Phex (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) in the Hyp mouse affects the expression and activity of neprilysin (NEP) and of endothelin-converting enzyme-like endopeptidase (ECEL1/DINE) in bone marrow stromal cells (BMSC) and osteoblasts (Ob). Total NEP-like activity was higher in Ob than in BMSC regardless of genotype, and Hyp cells showed higher activities than normal. Conditioned media (CM) from Hyp BMSC and Ob inhibited inorganic phosphate (Pi) uptake by mouse proximal tubule cells, and incubating Hyp Ob with phosphoramidon prevented the production of the inhibitor of renal Pi uptake. A linear relationship was observed between the NEP-like activity of Hyp and normal cells and the inhibition of Pi uptake. NEP and ECEL1/DINE mRNA levels were higher in Hyp cells than in normal cells, and in situ hybridization of ECEL1/DINE confirmed higher levels of expression in the Hyp mouse than in normal cells. In conclusion, we observed a correlation between the inhibition of Pi uptake by CM from Hyp cells and elevated NEP-like activities.

X-linked hypophosphatemia; Phex; putative inhibitor of renal phosphate uptake


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