Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation

Abstract Mesenchymal progenitors differentiate into several tissues including bone, cartilage, and adipose. Targeting these cells in vivo is challenging, making mesenchymal progenitor cell lines valuable tools to study tissue development. Mesenchymal stem cells (MSCs) can be isolated from humans and...

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Autores principales:	Matthew Prideaux, Christian S. Wright, Megan L. Noonan, Xin Yi, Erica L. Clinkenbeard, Elsa Mevel, Jonathan A. Wheeler, Sharon Byers, Asiri R. Wijenayaka, Stan Gronthos, Uma Sankar, Kenneth E. White, Gerald J. Atkins, William R. Thompson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f7398838cd214c8aba8d0dac83a09d11
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spelling	oai:doaj.org-article:f7398838cd214c8aba8d0dac83a09d112021-11-21T12:25:10ZGeneration of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation10.1038/s41598-021-02060-12045-2322https://doaj.org/article/f7398838cd214c8aba8d0dac83a09d112021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02060-1https://doaj.org/toc/2045-2322Abstract Mesenchymal progenitors differentiate into several tissues including bone, cartilage, and adipose. Targeting these cells in vivo is challenging, making mesenchymal progenitor cell lines valuable tools to study tissue development. Mesenchymal stem cells (MSCs) can be isolated from humans and animals; however, obtaining homogenous, responsive cells in a reproducible fashion is challenging. As such, we developed two mesenchymal progenitor cell (MPC) lines, MPC1 and MPC2, generated from bone marrow of male C57BL/6 mice. These cells were immortalized using the temperature sensitive large T-antigen, allowing for thermal control of proliferation and differentiation. Both MPC1 and MPC2 cells are capable of osteogenic, adipogenic, and chondrogenic differentiation. Under osteogenic conditions, both lines formed mineralized nodules, and stained for alizarin red and alkaline phosphatase, while expressing osteogenic genes including Sost, Fgf23, and Dmp1. Sost and Dmp1 mRNA levels were drastically reduced with addition of parathyroid hormone, thus recapitulating in vivo responses. MPC cells secreted intact (iFGF23) and C-terminal (cFGF23) forms of the endocrine hormone FGF23, which was upregulated by 1,25 dihydroxy vitamin D (1,25D). Both lines also rapidly entered the adipogenic lineage, expressing adipose markers after 4 days in adipogenic media. MPC cells were also capable of chondrogenic differentiation, displaying increased expression of cartilaginous genes including aggrecan, Sox9, and Comp. With the ability to differentiate into multiple mesenchymal lineages and mimic in vivo responses of key regulatory genes/proteins, MPC cells are a valuable model to study factors that regulate mesenchymal lineage allocation as well as the mechanisms that dictate transcription, protein modification, and secretion of these factors.Matthew PrideauxChristian S. WrightMegan L. NoonanXin YiErica L. ClinkenbeardElsa MevelJonathan A. WheelerSharon ByersAsiri R. WijenayakaStan GronthosUma SankarKenneth E. WhiteGerald J. AtkinsWilliam R. ThompsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew Prideaux Christian S. Wright Megan L. Noonan Xin Yi Erica L. Clinkenbeard Elsa Mevel Jonathan A. Wheeler Sharon Byers Asiri R. Wijenayaka Stan Gronthos Uma Sankar Kenneth E. White Gerald J. Atkins William R. Thompson Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
description	Abstract Mesenchymal progenitors differentiate into several tissues including bone, cartilage, and adipose. Targeting these cells in vivo is challenging, making mesenchymal progenitor cell lines valuable tools to study tissue development. Mesenchymal stem cells (MSCs) can be isolated from humans and animals; however, obtaining homogenous, responsive cells in a reproducible fashion is challenging. As such, we developed two mesenchymal progenitor cell (MPC) lines, MPC1 and MPC2, generated from bone marrow of male C57BL/6 mice. These cells were immortalized using the temperature sensitive large T-antigen, allowing for thermal control of proliferation and differentiation. Both MPC1 and MPC2 cells are capable of osteogenic, adipogenic, and chondrogenic differentiation. Under osteogenic conditions, both lines formed mineralized nodules, and stained for alizarin red and alkaline phosphatase, while expressing osteogenic genes including Sost, Fgf23, and Dmp1. Sost and Dmp1 mRNA levels were drastically reduced with addition of parathyroid hormone, thus recapitulating in vivo responses. MPC cells secreted intact (iFGF23) and C-terminal (cFGF23) forms of the endocrine hormone FGF23, which was upregulated by 1,25 dihydroxy vitamin D (1,25D). Both lines also rapidly entered the adipogenic lineage, expressing adipose markers after 4 days in adipogenic media. MPC cells were also capable of chondrogenic differentiation, displaying increased expression of cartilaginous genes including aggrecan, Sox9, and Comp. With the ability to differentiate into multiple mesenchymal lineages and mimic in vivo responses of key regulatory genes/proteins, MPC cells are a valuable model to study factors that regulate mesenchymal lineage allocation as well as the mechanisms that dictate transcription, protein modification, and secretion of these factors.
format	article
author	Matthew Prideaux Christian S. Wright Megan L. Noonan Xin Yi Erica L. Clinkenbeard Elsa Mevel Jonathan A. Wheeler Sharon Byers Asiri R. Wijenayaka Stan Gronthos Uma Sankar Kenneth E. White Gerald J. Atkins William R. Thompson
author_facet	Matthew Prideaux Christian S. Wright Megan L. Noonan Xin Yi Erica L. Clinkenbeard Elsa Mevel Jonathan A. Wheeler Sharon Byers Asiri R. Wijenayaka Stan Gronthos Uma Sankar Kenneth E. White Gerald J. Atkins William R. Thompson
author_sort	Matthew Prideaux
title	Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
title_short	Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
title_full	Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
title_fullStr	Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
title_full_unstemmed	Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
title_sort	generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f7398838cd214c8aba8d0dac83a09d11
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Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation

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