Ablation of Enpp6 Results in Transient Bone Hypomineralization.

Autor: Dillon S; The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh Midlothian UK., Suchacki K; Centre for Cardiovascular Science, Queen's Medical Research Institute University of Edinburgh Edinburgh UK., Hsu SN; The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh Midlothian UK., Stephen LA; The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh Midlothian UK., Wang R; Centre for Cardiovascular Science, Queen's Medical Research Institute University of Edinburgh Edinburgh UK., Cawthorn WP; Centre for Cardiovascular Science, Queen's Medical Research Institute University of Edinburgh Edinburgh UK., Stewart AJ; School of Medicine University of St Andrews St. Andrews UK., Nudelman F; School of Chemistry University of Edinburgh Edinburgh UK., Morton NM; Centre for Cardiovascular Science, Queen's Medical Research Institute University of Edinburgh Edinburgh UK., Farquharson C; The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh Midlothian UK.
Jazyk: angličtina
Zdroj: JBMR plus [JBMR Plus] 2020 Dec 08; Vol. 5 (2), pp. e10439. Date of Electronic Publication: 2020 Dec 08 (Print Publication: 2021).
DOI: 10.1002/jbm4.10439
Abstrakt: 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  < 0.05) that normalized by 12 weeks of age. Whole-bone cortical analysis also revealed significantly hypomineralized proximal bone in 4- but not 12-week-old Enpp6 -/- mice ( p  < 0.05) compared with WT animals. Back-scattered SEM revealed a failure in 4-week-old trabecular bone of mineralization foci to propagate. Static histomorphometry revealed increased osteoid volume ( p  > 0.01) and osteoid surface ( p  < 0.05), which recovered by 12 weeks but was not accompanied by changes in osteoblast or osteoclast number. This study is the first to characterize the skeletal phenotype of 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.
(© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.)
Databáze: MEDLINE
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