Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways
Arterial calcification, the deposition of calcium-phosphate crystals in the extracellular matrix, resembles physiological bone mineralization. It is well-known that extracellular nucleotides regulate bone homeostasis raising an emerging interest in the role of these molecules on arterial calcificati...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/20/7636 |
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| author | Britt Opdebeeck Isabel R. Orriss Ellen Neven Patrick C. D’Haese Anja Verhulst |
| author_facet | Britt Opdebeeck Isabel R. Orriss Ellen Neven Patrick C. D’Haese Anja Verhulst |
| author_sort | Britt Opdebeeck |
| collection | DOAJ |
| description | Arterial calcification, the deposition of calcium-phosphate crystals in the extracellular matrix, resembles physiological bone mineralization. It is well-known that extracellular nucleotides regulate bone homeostasis raising an emerging interest in the role of these molecules on arterial calcification. The purinergic independent pathway involves the enzymes ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs), ecto-nucleoside triphosphate diphosphohydrolases (NTPDases), 5′-nucleotidase and alkaline phosphatase. These regulate the production and breakdown of the calcification inhibitor—pyrophosphate and the calcification stimulator—inorganic phosphate, from extracellular nucleotides. Maintaining ecto-nucleotidase activities in a well-defined range is indispensable as enzymatic hyper- and hypo-expression has been linked to arterial calcification. The purinergic signaling dependent pathway focusses on the activation of purinergic receptors (P1, P2X and P2Y) by extracellular nucleotides. These receptors influence arterial calcification by interfering with the key molecular mechanisms underlying this pathology, including the osteogenic switch and apoptosis of vascular cells and possibly, by favoring the phenotypic switch of vascular cells towards an adipogenic phenotype, a recent, novel hypothesis explaining the systemic prevention of arterial calcification. Selective compounds influencing the activity of ecto-nucleotidases and purinergic receptors, have recently been developed to treat arterial calcification. However, adverse side-effects on bone mineralization are possible as these compounds reasonably could interfere with physiological bone mineralization. |
| first_indexed | 2024-03-10T15:35:47Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:35:47Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b3abac2d97054698a4124bdeb99eb01b2023-11-20T17:15:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120763610.3390/ijms21207636Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling PathwaysBritt Opdebeeck0Isabel R. Orriss1Ellen Neven2Patrick C. D’Haese3Anja Verhulst4Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerpen, BelgiumDepartment of Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UKLaboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerpen, BelgiumLaboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerpen, BelgiumLaboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerpen, BelgiumArterial calcification, the deposition of calcium-phosphate crystals in the extracellular matrix, resembles physiological bone mineralization. It is well-known that extracellular nucleotides regulate bone homeostasis raising an emerging interest in the role of these molecules on arterial calcification. The purinergic independent pathway involves the enzymes ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs), ecto-nucleoside triphosphate diphosphohydrolases (NTPDases), 5′-nucleotidase and alkaline phosphatase. These regulate the production and breakdown of the calcification inhibitor—pyrophosphate and the calcification stimulator—inorganic phosphate, from extracellular nucleotides. Maintaining ecto-nucleotidase activities in a well-defined range is indispensable as enzymatic hyper- and hypo-expression has been linked to arterial calcification. The purinergic signaling dependent pathway focusses on the activation of purinergic receptors (P1, P2X and P2Y) by extracellular nucleotides. These receptors influence arterial calcification by interfering with the key molecular mechanisms underlying this pathology, including the osteogenic switch and apoptosis of vascular cells and possibly, by favoring the phenotypic switch of vascular cells towards an adipogenic phenotype, a recent, novel hypothesis explaining the systemic prevention of arterial calcification. Selective compounds influencing the activity of ecto-nucleotidases and purinergic receptors, have recently been developed to treat arterial calcification. However, adverse side-effects on bone mineralization are possible as these compounds reasonably could interfere with physiological bone mineralization.https://www.mdpi.com/1422-0067/21/20/7636arterial calcificationpurinergic signalingpyrophosphateecto-nucleotidasesextracellular nucleotides |
| spellingShingle | Britt Opdebeeck Isabel R. Orriss Ellen Neven Patrick C. D’Haese Anja Verhulst Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways International Journal of Molecular Sciences arterial calcification purinergic signaling pyrophosphate ecto-nucleotidases extracellular nucleotides |
| title | Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways |
| title_full | Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways |
| title_fullStr | Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways |
| title_full_unstemmed | Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways |
| title_short | Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways |
| title_sort | extracellular nucleotides regulate arterial calcification by activating both independent and dependent purinergic receptor signaling pathways |
| topic | arterial calcification purinergic signaling pyrophosphate ecto-nucleotidases extracellular nucleotides |
| url | https://www.mdpi.com/1422-0067/21/20/7636 |
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