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Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides : The same functional effect mediated by different cellular mechanisms. / Patel, Jessal J; Zhu, Dongxing; Opdebeeck, Britt; D'Haese, Patrick; Millán, José L; Bourne, Lucie E; Wheeler-Jones, Caroline P D; Arnett, Timothy R; MacRae, Vicky E; Orriss, Isabel R.

In: Journal of Cellular Physiology, Vol. 233, No. 4, 04.10.2017, p. 3230-3243.

Research output: Contribution to journalArticlepeer-review

Harvard

Patel, JJ, Zhu, D, Opdebeeck, B, D'Haese, P, Millán, JL, Bourne, LE, Wheeler-Jones, CPD, Arnett, TR, MacRae, VE & Orriss, IR 2017, 'Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides: The same functional effect mediated by different cellular mechanisms', Journal of Cellular Physiology, vol. 233, no. 4, pp. 3230-3243. https://doi.org/10.1002/jcp.26166

APA

Patel, J. J., Zhu, D., Opdebeeck, B., D'Haese, P., Millán, J. L., Bourne, L. E., Wheeler-Jones, C. P. D., Arnett, T. R., MacRae, V. E., & Orriss, I. R. (2017). Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides: The same functional effect mediated by different cellular mechanisms. Journal of Cellular Physiology, 233(4), 3230-3243. https://doi.org/10.1002/jcp.26166

Vancouver

Author

Patel, Jessal J ; Zhu, Dongxing ; Opdebeeck, Britt ; D'Haese, Patrick ; Millán, José L ; Bourne, Lucie E ; Wheeler-Jones, Caroline P D ; Arnett, Timothy R ; MacRae, Vicky E ; Orriss, Isabel R. / Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides : The same functional effect mediated by different cellular mechanisms. In: Journal of Cellular Physiology. 2017 ; Vol. 233, No. 4. pp. 3230-3243.

Bibtex

@article{674fc96c564f4b4da50040ace0a120eb,
title = "Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides: The same functional effect mediated by different cellular mechanisms",
abstract = "Arterial medial calcification (AMC) is thought to share some outward similarities to skeletal mineralization and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. ATP and UTP have previously been shown to inhibit bone mineralization. This investigation compared the effects of extracellular nucleotides on calcification in VSMCs with those seen in osteoblasts. ATP, UTP and the ubiquitous mineralization inhibitor, pyrophosphate (PPi ), dose dependently inhibited VSMC calcification by ≤85%. Culture of VSMCs in calcifying conditions was associated with an increase in apoptosis; treatment with ATP, UTP, and PPi reduced apoptosis to levels seen in non-calcifying cells. Extracellular nucleotides had no effect on osteoblast viability. Basal alkaline phosphatase (TNAP) activity was over 100-fold higher in osteoblasts than VSMCs. ATP and UTP reduced osteoblast TNAP activity (≤50%) but stimulated VSMC TNAP activity (≤88%). The effects of extracellular nucleotides on VSMC calcification, cell viability and TNAP activity were unchanged by deletion or inhibition of the P2Y2 receptor. Conversely, the actions of ATP/UTP on bone mineralization and TNAP activity were attenuated in osteoblasts lacking the P2Y2 receptor. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) hydrolyses ATP and UTP to produce PPi . In both VSMCs and osteoblasts, deletion of NPP1 blunted the inhibitory effects of extracellular nucleotides suggesting involvement of P2 receptor independent pathways. Our results show that although the overall functional effect of extracellular nucleotides on AMC and bone mineralization is similar there are clear differences in the cellular mechanisms mediating these actions.",
keywords = "Adenosine Triphosphate/pharmacology, Alkaline Phosphatase/metabolism, Animals, Apoptosis/drug effects, Calcification, Physiologic/drug effects, Cell Survival/drug effects, Diphosphates/pharmacology, Extracellular Space/metabolism, Mice, Models, Biological, Muscle, Smooth, Vascular/drug effects, Myocytes, Smooth Muscle/metabolism, Nucleotides/pharmacology, Osteoblasts/drug effects, Phosphoric Diester Hydrolases/deficiency, Pyrophosphatases/deficiency, Receptors, Purinergic P2/metabolism, Tunica Media/pathology, Uridine Triphosphate/pharmacology, Vascular Calcification/pathology",
author = "Patel, {Jessal J} and Dongxing Zhu and Britt Opdebeeck and Patrick D'Haese and Mill{\'a}n, {Jos{\'e} L} and Bourne, {Lucie E} and Wheeler-Jones, {Caroline P D} and Arnett, {Timothy R} and MacRae, {Vicky E} and Orriss, {Isabel R}",
note = "{\textcopyright} 2017 Wiley Periodicals, Inc.",
year = "2017",
month = oct,
day = "4",
doi = "10.1002/jcp.26166",
language = "English",
volume = "233",
pages = "3230--3243",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides

T2 - The same functional effect mediated by different cellular mechanisms

AU - Patel, Jessal J

AU - Zhu, Dongxing

AU - Opdebeeck, Britt

AU - D'Haese, Patrick

AU - Millán, José L

AU - Bourne, Lucie E

AU - Wheeler-Jones, Caroline P D

AU - Arnett, Timothy R

AU - MacRae, Vicky E

AU - Orriss, Isabel R

N1 - © 2017 Wiley Periodicals, Inc.

PY - 2017/10/4

Y1 - 2017/10/4

N2 - Arterial medial calcification (AMC) is thought to share some outward similarities to skeletal mineralization and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. ATP and UTP have previously been shown to inhibit bone mineralization. This investigation compared the effects of extracellular nucleotides on calcification in VSMCs with those seen in osteoblasts. ATP, UTP and the ubiquitous mineralization inhibitor, pyrophosphate (PPi ), dose dependently inhibited VSMC calcification by ≤85%. Culture of VSMCs in calcifying conditions was associated with an increase in apoptosis; treatment with ATP, UTP, and PPi reduced apoptosis to levels seen in non-calcifying cells. Extracellular nucleotides had no effect on osteoblast viability. Basal alkaline phosphatase (TNAP) activity was over 100-fold higher in osteoblasts than VSMCs. ATP and UTP reduced osteoblast TNAP activity (≤50%) but stimulated VSMC TNAP activity (≤88%). The effects of extracellular nucleotides on VSMC calcification, cell viability and TNAP activity were unchanged by deletion or inhibition of the P2Y2 receptor. Conversely, the actions of ATP/UTP on bone mineralization and TNAP activity were attenuated in osteoblasts lacking the P2Y2 receptor. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) hydrolyses ATP and UTP to produce PPi . In both VSMCs and osteoblasts, deletion of NPP1 blunted the inhibitory effects of extracellular nucleotides suggesting involvement of P2 receptor independent pathways. Our results show that although the overall functional effect of extracellular nucleotides on AMC and bone mineralization is similar there are clear differences in the cellular mechanisms mediating these actions.

AB - Arterial medial calcification (AMC) is thought to share some outward similarities to skeletal mineralization and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. ATP and UTP have previously been shown to inhibit bone mineralization. This investigation compared the effects of extracellular nucleotides on calcification in VSMCs with those seen in osteoblasts. ATP, UTP and the ubiquitous mineralization inhibitor, pyrophosphate (PPi ), dose dependently inhibited VSMC calcification by ≤85%. Culture of VSMCs in calcifying conditions was associated with an increase in apoptosis; treatment with ATP, UTP, and PPi reduced apoptosis to levels seen in non-calcifying cells. Extracellular nucleotides had no effect on osteoblast viability. Basal alkaline phosphatase (TNAP) activity was over 100-fold higher in osteoblasts than VSMCs. ATP and UTP reduced osteoblast TNAP activity (≤50%) but stimulated VSMC TNAP activity (≤88%). The effects of extracellular nucleotides on VSMC calcification, cell viability and TNAP activity were unchanged by deletion or inhibition of the P2Y2 receptor. Conversely, the actions of ATP/UTP on bone mineralization and TNAP activity were attenuated in osteoblasts lacking the P2Y2 receptor. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) hydrolyses ATP and UTP to produce PPi . In both VSMCs and osteoblasts, deletion of NPP1 blunted the inhibitory effects of extracellular nucleotides suggesting involvement of P2 receptor independent pathways. Our results show that although the overall functional effect of extracellular nucleotides on AMC and bone mineralization is similar there are clear differences in the cellular mechanisms mediating these actions.

KW - Adenosine Triphosphate/pharmacology

KW - Alkaline Phosphatase/metabolism

KW - Animals

KW - Apoptosis/drug effects

KW - Calcification, Physiologic/drug effects

KW - Cell Survival/drug effects

KW - Diphosphates/pharmacology

KW - Extracellular Space/metabolism

KW - Mice

KW - Models, Biological

KW - Muscle, Smooth, Vascular/drug effects

KW - Myocytes, Smooth Muscle/metabolism

KW - Nucleotides/pharmacology

KW - Osteoblasts/drug effects

KW - Phosphoric Diester Hydrolases/deficiency

KW - Pyrophosphatases/deficiency

KW - Receptors, Purinergic P2/metabolism

KW - Tunica Media/pathology

KW - Uridine Triphosphate/pharmacology

KW - Vascular Calcification/pathology

UR - http://www.scopus.com/inward/record.url?scp=85038889743&partnerID=8YFLogxK

U2 - 10.1002/jcp.26166

DO - 10.1002/jcp.26166

M3 - Article

C2 - 28976001

VL - 233

SP - 3230

EP - 3243

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 4

ER -