SPR4-peptide alters bone metabolism of normal and HYP mice.

ABSTRACT:

Context

ASARM-peptides are substrates and ligands for PHEX, the gene responsible for X-linked hypophosphatemic rickets (HYP). PHEX binds to the DMP1-ASARM-motif to form a trimeric-complex with α5β3-integrin on the osteocyte surface and this suppresses FGF23 expression. ASARM-peptide disruption of this complex increases FGF23 expression. We used a 4.2kDa peptide (SPR4) that binds to ASARM-peptide and ASARM-motif to study DMP1-PHEX interactions and to assess SPR4 for treating inherited hypophosphatemic rickets.

Design

Subcutaneously transplanted osmotic pumps were used to infuse SPR4-peptide or vehicle into wild-type mice (WT) and HYP-mice for 4 weeks.

Results

Asymmetrically distributed mineralization defects occurred with WT-SPR4 femurs. Specifically, SPR4 induced nega

SUBMITTER: Zelenchuk LV 

PROVIDER: S-EPMC4342984 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature