Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells

Calcium is a ubiquitous intracellular messenger that has a crucial role in determining the proliferation, differentiation, and functions of multipotent mesenchymal stem cells (MSCs). Our study is aimed at elucidating the influence of genetically manipulating Ca2+ release-activated Ca2+ (CRAC) channe...

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Main Authors: Shuang Liu, Minae Takahashi, Takeshi Kiyoi, Kensuke Toyama, Masaki Mogi
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/7510214
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author Shuang Liu
Minae Takahashi
Takeshi Kiyoi
Kensuke Toyama
Masaki Mogi
author_facet Shuang Liu
Minae Takahashi
Takeshi Kiyoi
Kensuke Toyama
Masaki Mogi
author_sort Shuang Liu
collection DOAJ
description Calcium is a ubiquitous intracellular messenger that has a crucial role in determining the proliferation, differentiation, and functions of multipotent mesenchymal stem cells (MSCs). Our study is aimed at elucidating the influence of genetically manipulating Ca2+ release-activated Ca2+ (CRAC) channel-mediated intercellular Ca2+ signaling on the multipotency of MSCs. The abilities of genetically engineered MSCs, including CRAC-overexpressing and CRAC-knockout MSCs, to differentiate into multiple mesenchymal lineages, including adipogenic, osteogenic, and chondrogenic lineages, were evaluated. CRAC channel-mediated Ca2+ influx into these cells was regulated, and the differentiation fate of MSCs was modified. Upregulation of intracellular Ca2+ signals attenuated the adipogenic differentiation ability and slightly increased the osteogenic differentiation potency of MSCs, whereas downregulation of CRACM1 expression promoted chondrogenic differentiation potency. The findings demonstrated the effects of genetically manipulating MSCs by targeting CRACM1. CRAC-modified MSCs had distinct differentiation fates to adipocytes, osteoblasts, and chondrocytes. To aid in the clinical implementation of tissue engineering strategies for joint regeneration, these data may allow us to identify prospective factors for effective treatments and could maximize the therapeutic potential of MSC-based transplantation.
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issn 2314-8861
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language English
publishDate 2019-01-01
publisher Wiley
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series Journal of Immunology Research
spelling doaj-art-a7241fffafc4420dbeb450cba85d9b122025-02-03T01:13:00ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/75102147510214Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem CellsShuang Liu0Minae Takahashi1Takeshi Kiyoi2Kensuke Toyama3Masaki Mogi4Department of Pharmacology, Ehime University Graduate School of Medicine, Shitsugawa, Toon-shi, Ehime 791-0295, JapanDepartment of Pharmacology, Ehime University Graduate School of Medicine, Shitsugawa, Toon-shi, Ehime 791-0295, JapanDepartment of Bioscience, Integrated Center for Sciences, Ehime University, Shitsukawa, Toon-shi, Ehime 791-0295, JapanDepartment of Pharmacology, Ehime University Graduate School of Medicine, Shitsugawa, Toon-shi, Ehime 791-0295, JapanDepartment of Pharmacology, Ehime University Graduate School of Medicine, Shitsugawa, Toon-shi, Ehime 791-0295, JapanCalcium is a ubiquitous intracellular messenger that has a crucial role in determining the proliferation, differentiation, and functions of multipotent mesenchymal stem cells (MSCs). Our study is aimed at elucidating the influence of genetically manipulating Ca2+ release-activated Ca2+ (CRAC) channel-mediated intercellular Ca2+ signaling on the multipotency of MSCs. The abilities of genetically engineered MSCs, including CRAC-overexpressing and CRAC-knockout MSCs, to differentiate into multiple mesenchymal lineages, including adipogenic, osteogenic, and chondrogenic lineages, were evaluated. CRAC channel-mediated Ca2+ influx into these cells was regulated, and the differentiation fate of MSCs was modified. Upregulation of intracellular Ca2+ signals attenuated the adipogenic differentiation ability and slightly increased the osteogenic differentiation potency of MSCs, whereas downregulation of CRACM1 expression promoted chondrogenic differentiation potency. The findings demonstrated the effects of genetically manipulating MSCs by targeting CRACM1. CRAC-modified MSCs had distinct differentiation fates to adipocytes, osteoblasts, and chondrocytes. To aid in the clinical implementation of tissue engineering strategies for joint regeneration, these data may allow us to identify prospective factors for effective treatments and could maximize the therapeutic potential of MSC-based transplantation.http://dx.doi.org/10.1155/2019/7510214
spellingShingle Shuang Liu
Minae Takahashi
Takeshi Kiyoi
Kensuke Toyama
Masaki Mogi
Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells
Journal of Immunology Research
title Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells
title_full Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells
title_fullStr Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells
title_full_unstemmed Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells
title_short Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells
title_sort genetic manipulation of calcium release activated calcium channel 1 modulates the multipotency of human cartilage derived mesenchymal stem cells
url http://dx.doi.org/10.1155/2019/7510214
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