Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice.

Autor: Roberts FL; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK., Rashdan NA; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK., Phadwal K; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK., Markby GR; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK., Dillon S; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK., Zoll J; Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA., Berger J; Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA., Milne E; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK., Orriss IR; Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, UK., Karsenty G; Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA., Le Saux O; Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA., Morton NM; Centre for Cardiovascular Science, The Queen's Medical Research Institute, The College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK., Farquharson C; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK., MacRae VE; Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2021 Jun; Vol. 236 (6), pp. 4614-4624. Date of Electronic Publication: 2020 Dec 10.
DOI: 10.1002/jcp.30194
Abstrakt: Supraphysiological levels of the osteoblast-enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase-1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast-specific Enpp1 ablation on skeletal structure and metabolic phenotype in mice. Female, but not male, 6-week-old mice lacking osteoblast NPP1 expression (osteoblast-specific knockout [KO]) exhibited increased femoral bone volume or total volume (17.50% vs. 11.67%; p < .01), and reduced trabecular spacing (0.187 vs. 0.157 mm; p < .01) compared with floxed (control) mice. Furthermore, an enhanced ability of isolated osteoblasts from the osteoblast-specific KO to calcify their matrix in vitro compared to fl/fl osteoblasts was observed (p < .05). Male osteoblast-specific KO and fl/fl mice showed comparable glucose and insulin tolerance despite increased levels of insulin-sensitizing under-carboxylated osteocalcin (195% increase; p < .05). However, following high-fat-diet challenge, osteoblast-specific KO mice showed impaired glucose and insulin tolerance compared with fl/fl mice. These data highlight a crucial local role for osteoblast NPP1 in skeletal development and a secondary metabolic impact that predominantly maintains insulin sensitivity.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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