Bone Abstracts

ASARM peptide (acidic, serine- and aspartate-rich motif) and osteopontin (OPN) fragments accumulate in X-linked hypophosphatemia patients and/or in the Hyp mouse model and, when phosphorylated, potently inhibit mineralization in osteoblast cultures. To investigate this inhibition, we modeled the binding to hydroxyapatite of the human OPN-ASARM peptide (DDSHQSDESHHSDESDEL) using RosettaSurface computational simulations. Peptide binding to hydroxyapatite atomic planes constructe...

Proprotein convertase PC5/6 (Pcsk5) is expressed in mouse bone and Pcsk5 epiblast-specific conditional knockout mice have a bone phenotype displaying small size, delayed ossification and additional thoracic segments and ribs. Some features are attributed to growth and developmental factor 11 (GDF11) – a known substrate for PC5/6 – while the delayed mineralization has yet to be explained. Osteopontin (OPN) is a bone matrix protein with roles in miner...

Mutations in the PHEX gene cause X-linked familial hypophosphatemic rickets (XLH) with severe bone (osteomalacia) and tooth abnormalities being the distinguishing features of this disease. The PHEX mutations lead to an increase in ASARM peptides (acidic serine- and aspartate-rich motif) and osteopontin fragments which inhibit bone extracellular matrix mineralization. MEPE-derived ASARM has been shown to accumulate in tooth dentin of patients with XLH where it may impair dentin...