Elevated Skeletal Osteopontin Levels Contribute to the Hypophosphatasia Phenotype in <i>Akp2</i>−/− Mice

Abstract

Deletion of both Akp2 and Opn can partially rescue the hypomineralized phenotype of Akp2(-/-) mice. However, these double knockout mice do not display corrected ePP(i) levels, and we conclude that regulation of hydroxyapatite deposition requires the coordinated actions of both PP(i) and OPN and that the hypophosphatasia phenotype in Akp2(-/-) mice results from the combined inhibitory action of increased levels of both ePP(i) and OPN. Our data also suggest that the ePP(i)-mediated regulation of OPN and the OPN-mediated regulation of ePP(i) are linked counterregulatory mechanisms that control the concentrations of these two important mineralization inhibitors, OPN and ePP(i).