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Am J Physiol Cell Physiol (August 14, 2002). doi:10.1152/ajpcell.00135.2002
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Articles in PresS, published online ahead of print August 14, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00135.2002
Submitted on March 25, 2002
Accepted on July 3, 2002

Abnormal neutral endopeptidase-like activities in Hyp mouse bone cells: possible relationship with renal phosphate transport

Stephanie G Dubois1, Andrea F Ruchon2, Aline Delalandre1, Guy Boileau2, and Daniel Lajeunesse1*

1 Unite de recherche en Arthrose, CRCHUM - Hopital Notre-Dame, Montreal, Quebec, Canada
2 Biochimie, Universite de Montreal, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: daniel.lajeunesse{at}umontreal.ca.

We investigated if 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 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 compared to normal and in situ hybridization of ECEL1/DINE confirmed higher levels of expression in the Hyp mouse compared to normal. In conclusion, we observed a correlation between the inhibition of Pi uptake by CM from Hyp cells and elevated NEP-like activities.




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