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Special Issue "The Role of Tissue-Nonspecific Alkaline Phosphatase in Inflammation and Metabolic Syndrome"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 December 2020).

Special Issue Editor

Prof. Dr. David Magne
Website
Guest Editor
MEM2 team: Metabolism, Enzymes and Molecular Mechanisms, Institute of Molecular and Supramolecular Chemistry and Biochemistry, ICBMS UMR CNRS 5246 University Lyon 1, 69622 Villeurbanne cedex, France
Interests: Vascular calcification; pathological bone formation; tissue-nonspecific alkaline phosphatase; inflammation; mineralization

Special Issue Information

Dear Colleagues,

Tissue-nonspecific alkaline phosphatase (TNAP) is mainly known for its necessary function during bone mineralization, due to the dephosphorylation of the mineralization inhibitor inorganic pyrophosphate (PPi). TNAP is however a relatively ubiquitous enzyme expressed in liver, kidney or brain that is present in the blood, both as a soluble form and at the membrane of neutrophils. Serum TNAP activity is elevated in individuals with metabolic syndrome and is associated with their increased mortality risk. This association may result from the function of TNAP in inflammation, relying on the dephosphorylation of adenosine nucleotides and lipopolysaccharide. It may also rely on the stimulation of cardiovascular calcification resulting from PPi hydrolysis in the blood and/or cardiovascular tissues.

This Special Issue of IJMS aims to cover recent findings on the regulation of TNAP during metabolic syndrome, on its inflammatory functions, and the consequences of its activation on cardiovascular mortality. Original research articles, comprehensive reviews, and short communications are all welcome.

Prof. Dr. David Magne
Guest Editor

Manuscript Submission Information

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Keywords

  • tissue-nonspecific alkaline phosphatase (TNAP)
  • inflammation
  • adenosine nucleotides
  • lipopolysaccharide
  • metabolic syndrome
  • vascular calcification

Published Papers (3 papers)

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Research

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Open AccessArticle
Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production
Int. J. Mol. Sci. 2021, 22(3), 1140; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031140 - 24 Jan 2021
Abstract
Tissue nonspecific alkaline phosphatase (TNAP/Alpl) is associated with cell stemness; however, the function of TNAP in mesenchymal progenitor cells remains largely unknown. In this study, we aimed to establish an essential role for TNAP in bone and muscle progenitor cells. We [...] Read more.
Tissue nonspecific alkaline phosphatase (TNAP/Alpl) is associated with cell stemness; however, the function of TNAP in mesenchymal progenitor cells remains largely unknown. In this study, we aimed to establish an essential role for TNAP in bone and muscle progenitor cells. We investigated the impact of TNAP deficiency on bone formation, mineralization, and differentiation of bone marrow stromal cells. We also pursued studies of proliferation, mitochondrial function and ATP levels in TNAP deficient bone and muscle progenitor cells. We find that TNAP deficiency decreases trabecular bone volume fraction and trabeculation in addition to decreased mineralization. We also find that Alpl−/− mice (global TNAP knockout mice) exhibit muscle and motor coordination deficiencies similar to those found in individuals with hypophosphatasia (TNAP deficiency). Subsequent studies demonstrate diminished proliferation, with mitochondrial hyperfunction and increased ATP levels in TNAP deficient bone and muscle progenitor cells, plus intracellular expression of TNAP in TNAP+ cranial osteoprogenitors, bone marrow stromal cells, and skeletal muscle progenitor cells. Together, our results indicate that TNAP functions inside bone and muscle progenitor cells to influence mitochondrial respiration and ATP production. Future studies are required to establish mechanisms by which TNAP influences mitochondrial function and determine if modulation of TNAP can alter mitochondrial respiration in vivo. Full article
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Open AccessArticle
Deficiency in Tissue Non-Specific Alkaline Phosphatase Leads to Steatohepatitis in Mice Fed a High Fat Diet Similar to That Produced by a Methionine and Choline Deficient Diet
Int. J. Mol. Sci. 2021, 22(1), 51; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010051 - 23 Dec 2020
Abstract
The liver expresses tissue-nonspecific alkaline phosphatase (TNAP), which may participate in the defense against bacterial components, in cell regulation as part of the purinome or in bile secretion, among other roles. We aimed to study the role of TNAP in the development of [...] Read more.
The liver expresses tissue-nonspecific alkaline phosphatase (TNAP), which may participate in the defense against bacterial components, in cell regulation as part of the purinome or in bile secretion, among other roles. We aimed to study the role of TNAP in the development of hepatosteatosis. TNAP+/− haplodeficient and wild type (WT) mice were fed a control diet (containing 10% fat w/w) or the same diet deficient in methionine and choline (MCD diet). The MCD diet induced substantial weight loss together with hepatic steatosis and increased alanine aminotransferase (ALT) plasma levels, but no differences in IL-6, TNF, insulin or resistin. There were no substantial differences between TNAP+/− and WT mice fed the MCD diet. In turn, TNAP+/− mice receiving the control diet presented hepatic steatosis with alterations in metabolic parameters very similar to those induced by the MCD diet. Nevertheless, no weight loss, increased ALT plasma levels or hypoglycemia were observed. These mice also presented increased levels of liver TNF and systemic resistin and glucagon compared to WT mice. The phenotype of TNAP+/− mice fed a standard diet was normal. In conclusion, TNAP haplodeficiency induces steatosis comparable to that produced by a MCD diet when fed a control diet. Full article
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Review

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Open AccessReview
TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism
Int. J. Mol. Sci. 2021, 22(2), 919; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020919 - 18 Jan 2021
Abstract
This review summarizes important information on the ectoenzyme tissue-nonspecific alkaline phosphatase (TNAP) and gives a brief insight into the symptoms, diagnostics, and treatment of the rare disease Hypophosphatasia (HPP), which is resulting from mutations in the TNAP encoding ALPL gene. We emphasize the [...] Read more.
This review summarizes important information on the ectoenzyme tissue-nonspecific alkaline phosphatase (TNAP) and gives a brief insight into the symptoms, diagnostics, and treatment of the rare disease Hypophosphatasia (HPP), which is resulting from mutations in the TNAP encoding ALPL gene. We emphasize the role of TNAP beyond its well-known contribution to mineralization processes. Therefore, above all, the impact of the enzyme on central molecular processes in the nervous system and on inflammation is presented here. Full article
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