Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm

Alkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification. In humans, four forms of ALP cDNA have been cloned, among which t...

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Main Authors: Masahiro Sato, Issei Saitoh, Yuki Kiyokawa, Yoko Iwase, Naoko Kubota, Natsumi Ibano, Hirofumi Noguchi, Youichi Yamasaki, Emi Inada
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/10/12/3338
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author Masahiro Sato
Issei Saitoh
Yuki Kiyokawa
Yoko Iwase
Naoko Kubota
Natsumi Ibano
Hirofumi Noguchi
Youichi Yamasaki
Emi Inada
author_facet Masahiro Sato
Issei Saitoh
Yuki Kiyokawa
Yoko Iwase
Naoko Kubota
Natsumi Ibano
Hirofumi Noguchi
Youichi Yamasaki
Emi Inada
author_sort Masahiro Sato
collection DOAJ
description Alkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification. In humans, four forms of ALP cDNA have been cloned, among which tissue-nonspecific ALP (TNSALP) (TNSALP) is widely distributed in the liver, bone, and kidney, making it an important marker in clinical and basic research. Interestingly, TNSALP is highly expressed in juvenile cells, such as pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells (iPSCs)) and somatic stem cells (i.e., neuronal stem cells and bone marrow mesenchymal stem cells). Hypophosphatasia is a genetic disorder causing defects in bone and tooth development as well as neurogenesis. Mutations in the gene coding for TNSALP are thought to be responsible for the abnormalities, suggesting the essential role of TNSALP in these events. Moreover, a reverse-genetics-based study using mice revealed that TNSALP is important in bone and tooth development as well as neurogenesis. However, little is known about the role of TNSALP in the maintenance and differentiation of juvenile cells. Recently, it was reported that cells enriched with TNSALP are more easily reprogrammed into iPSCs than those with less TNSALP. Furthermore, in bone marrow stem cells, ALP could function as a “signal regulator” deciding the fate of these cells. In this review, we summarize the properties of ALP and the background of ALP gene analysis and its manipulation, with a special focus on the potential role of TNSALP in the generation (and possibly maintenance) of juvenile cells.
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spelling doaj.art-93492cf2fe75489e8600d76e203f2cc42023-11-23T07:36:24ZengMDPI AGCells2073-44092021-11-011012333810.3390/cells10123338Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New ParadigmMasahiro Sato0Issei Saitoh1Yuki Kiyokawa2Yoko Iwase3Naoko Kubota4Natsumi Ibano5Hirofumi Noguchi6Youichi Yamasaki7Emi Inada8Department of Genome Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, JapanDepartment of Pediatric Dentistry, Asahi University School of Dentistry, Gifu 501-0296, JapanDepartment of Pediatric Dentistry, Asahi University School of Dentistry, Gifu 501-0296, JapanDepartment of Dentistry for the Disabled, Asahi University School of Dentistry, Gifu 501-0296, JapanDepartment of Pediatric Dentistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanDepartment of Pediatric Dentistry, Asahi University School of Dentistry, Gifu 501-0296, JapanDepartment of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, JapanDepartment of Pediatric Dentistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanDepartment of Pediatric Dentistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanAlkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification. In humans, four forms of ALP cDNA have been cloned, among which tissue-nonspecific ALP (TNSALP) (TNSALP) is widely distributed in the liver, bone, and kidney, making it an important marker in clinical and basic research. Interestingly, TNSALP is highly expressed in juvenile cells, such as pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells (iPSCs)) and somatic stem cells (i.e., neuronal stem cells and bone marrow mesenchymal stem cells). Hypophosphatasia is a genetic disorder causing defects in bone and tooth development as well as neurogenesis. Mutations in the gene coding for TNSALP are thought to be responsible for the abnormalities, suggesting the essential role of TNSALP in these events. Moreover, a reverse-genetics-based study using mice revealed that TNSALP is important in bone and tooth development as well as neurogenesis. However, little is known about the role of TNSALP in the maintenance and differentiation of juvenile cells. Recently, it was reported that cells enriched with TNSALP are more easily reprogrammed into iPSCs than those with less TNSALP. Furthermore, in bone marrow stem cells, ALP could function as a “signal regulator” deciding the fate of these cells. In this review, we summarize the properties of ALP and the background of ALP gene analysis and its manipulation, with a special focus on the potential role of TNSALP in the generation (and possibly maintenance) of juvenile cells.https://www.mdpi.com/2073-4409/10/12/3338alkaline phosphatasetissue-nonspecific alkaline phosphatasepluripotent stem cellssomatic stem cellssignal regulatorjuvenile cells
spellingShingle Masahiro Sato
Issei Saitoh
Yuki Kiyokawa
Yoko Iwase
Naoko Kubota
Natsumi Ibano
Hirofumi Noguchi
Youichi Yamasaki
Emi Inada
Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm
Cells
alkaline phosphatase
tissue-nonspecific alkaline phosphatase
pluripotent stem cells
somatic stem cells
signal regulator
juvenile cells
title Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm
title_full Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm
title_fullStr Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm
title_full_unstemmed Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm
title_short Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm
title_sort tissue nonspecific alkaline phosphatase a possible mediator of cell maturation towards a new paradigm
topic alkaline phosphatase
tissue-nonspecific alkaline phosphatase
pluripotent stem cells
somatic stem cells
signal regulator
juvenile cells
url https://www.mdpi.com/2073-4409/10/12/3338
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