Ablation of Enpp6 Results in Transient Bone Hypomineralization.

ABSTRACT: Biomineralization is a fundamental process key to the development of the skeleton. The phosphatase orphan phosphatase 1 (PHOSPHO1), which likely functions within extracellular matrix vesicles, has emerged as a critical regulator of biomineralization. However, the biochemical pathways that generate intravesicular PHOSPHO1 substrates are currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6) is an upstream source of the PHOSPHO1 substrate. To test this, we characterized skeletal phenotypes of mice homozygous for a targeted deletion of Enpp6 (Enpp6 ^-/- ). Micro-computed tomography of the trabecular compartment revealed transient hypomineralization in Enpp6 ^-/- tibias (p?Enpp6 ^-/- mice (p?p?>?0.01) and osteoid surface (p?Enpp6 ^-/- mice, revealing transient hypomineralization in young animals compared with WT controls. These data suggest that ENPP6 is important for bone mineralization and may function upstream of PHOSPHO1 as a novel means of generating its substrates inside matrix vesicles. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

SUBMITTER: Dillon S 

PROVIDER: S-EPMC7872340 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature