Ablation of Enpp6 results in transient bone hypomineralization

Scott Dillon; Karla Oldknow; Shun-Neng Hsu; Louise Stephen; Rongling Wang; William P Cawthorn; Alan J.  Stewart; Fabio Nudelman; Nicholas M Morton; Colin Farquharson

doi:10.1002/jbm4.10439

Ablation of Enpp6 results in transient bone hypomineralization

Scott Dillon, Karla Oldknow, Shun-Neng Hsu, Louise Stephen, Rongling Wang, William P Cawthorn, Alan J. Stewart, Fabio Nudelman, Nicholas M Morton, Colin Farquharson

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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. The biochemical pathways which generate intravesicular PHOSPHO1 substrates are however currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase (ENPP6) is an upstream source of 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‒/‒ tibiae (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 to wild-type animals. Backscattered scanning electron microscopy revealed a failure in 4-week-old trabecular bone

Original language	English
Journal	JBMR Plus
Early online date	24 Nov 2020
DOIs	https://doi.org/10.1002/jbm4.10439
Publication status	E-pub ahead of print - 24 Nov 2020

Keywords / Materials (for Non-textual outputs)

ENPP6
PHOSPHO1
Matrix mineralization
Osteoblast
Matrix vesicle

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10.1002/jbm4.10439

jbm4.10439Final published version, 2.11 MBLicence: Creative Commons: Attribution (CC-BY)

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@article{75da1302fd204df4b174acbf6cc7bc24,

title = "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. The biochemical pathways which generate intravesicular PHOSPHO1 substrates are however currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase (ENPP6) is an upstream source of 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‒/‒ tibiae (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 to wild-type animals. Backscattered scanning electron microscopy revealed a failure in 4-week-old trabecular bone",

keywords = "ENPP6, PHOSPHO1, Matrix mineralization, Osteoblast, Matrix vesicle",

author = "Scott Dillon and Karla Oldknow and Shun-Neng Hsu and Louise Stephen and Rongling Wang and Cawthorn, {William P} and Stewart, {Alan J.} and Fabio Nudelman and Morton, {Nicholas M} and Colin Farquharson",

year = "2020",

month = nov,

day = "24",

doi = "10.1002/jbm4.10439",

language = "English",

journal = "JBMR Plus",

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publisher = "Wiley-Blackwell",

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T1 - Ablation of Enpp6 results in transient bone hypomineralization

AU - Dillon, Scott

AU - Oldknow, Karla

AU - Hsu, Shun-Neng

AU - Stephen, Louise

AU - Wang, Rongling

AU - Cawthorn, William P

AU - Stewart, Alan J.

AU - Nudelman, Fabio

AU - Morton, Nicholas M

AU - Farquharson, Colin

PY - 2020/11/24

Y1 - 2020/11/24

N2 - 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. The biochemical pathways which generate intravesicular PHOSPHO1 substrates are however currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase (ENPP6) is an upstream source of 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‒/‒ tibiae (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 to wild-type animals. Backscattered scanning electron microscopy revealed a failure in 4-week-old trabecular bone

AB - 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. The biochemical pathways which generate intravesicular PHOSPHO1 substrates are however currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase (ENPP6) is an upstream source of 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‒/‒ tibiae (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 to wild-type animals. Backscattered scanning electron microscopy revealed a failure in 4-week-old trabecular bone

KW - ENPP6

KW - PHOSPHO1

KW - Matrix mineralization

KW - Osteoblast

KW - Matrix vesicle

U2 - 10.1002/jbm4.10439

DO - 10.1002/jbm4.10439

M3 - Article

SN - 2473-4039

JO - JBMR Plus

JF - JBMR Plus

ER -

Ablation of Enpp6 results in transient bone hypomineralization

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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