Ablation of osteopontin improves the skeletal phenotype of phospho1(-/-) mice.

ABSTRACT: PHOSPHO1 and tissue-nonspecific alkaline phosphatase (TNAP) have nonredundant functions during skeletal mineralization. Although TNAP deficiency (Alpl(-/-) mice) leads to hypophosphatasia, caused by accumulation of the mineralization inhibitor inorganic pyrophosphate (PPi ), comparably elevated levels of PPi in Phospho1(-/-) mice do not explain their stunted growth, spontaneous fractures, bowed long bones, osteomalacia, and scoliosis. We have previously shown that elevated PPi in Alpl(-/-) mice is accompanied by elevated osteopontin (OPN), another potent mineralization inhibitor, and that the amount of OPN correlates with the severity of hypophosphatasia in mice. Here we demonstrate that plasma OPN is elevated and OPN expression is upregulated in the skeleton, particularly in the vertebrae

SUBMITTER: Yadav MC 

PROVIDER: S-EPMC5247257 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature