High-dose oral pyrophosphate inhibits connective tissue calcification in Abcc6 null mice but may affect bone structure.

ABSTRACT: Pseudoxanthoma elasticum (PXE) is a rare inherited disorder marked by abnormal calcium phosphate deposition in soft connective tissues, particularly the skin, arteries, and eyes. It is caused by inactivating mutations in the ABCC6 gene, which encodes a hepatic efflux transporter. Loss of ABCC6 function leads to reduced plasma levels of pyrophosphate (PPi), a key inhibitor of calcification, thereby promoting ectopic mineralization. Oral PPi therapy has emerged as a potential treatment, but its effectiveness is uncertain. Most ingested PPi is hydrolyzed in the gut to inorganic phosphate, which may worsen calcification. Moreover, its impact on mineralized tissues remains largely unexplored. Abcc6-/- mice closely mimic human PXE and are widely used in preclinical studies. Althoug

SUBMITTER: Rajpar I 

PROVIDER: S-EPMC12861082 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature