Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/133821
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Type: | Journal article |
Title: | Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation |
Author: | Prideaux, M. Wright, C.S. Noonan, M.L. Yi, X. Clinkenbeard, E.L. Mevel, E. Wheeler, J.A. Byers, S. Wijenayaka, A.R. Gronthos, S. Sankar, U. White, K.E. Atkins, G.J. Thompson, W.R. |
Citation: | Scientific Reports, 2021; 11(1):22593-1-22593-16 |
Publisher: | Nature Publishing Group |
Issue Date: | 2021 |
ISSN: | 2045-2322 2045-2322 |
Statement of Responsibility: | 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 |
Abstract: | Mesenchymal progenitors diferentiate 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 diferentiation. Both MPC1 and MPC2 cells are capable of osteogenic, adipogenic, and chondrogenic diferentiation. 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 diferentiation, displaying increased expression of cartilaginous genes including aggrecan, Sox9, and Comp. With the ability to diferentiate 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 modifcation, and secretion of these factors. |
Keywords: | Cell Line Adipocytes Chondrocytes Osteocytes Mesenchymal Stem Cells Animals Mice, Inbred C57BL Mice RNA, Messenger Cell Culture Techniques Immunophenotyping Cell Differentiation Cell Proliferation Cell Lineage Male Fibroblast Growth Factor-23 |
Rights: | © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
DOI: | 10.1038/s41598-021-02060-1 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1106029 http://purl.org/au-research/grants/nhmrc/1080806 |
Published version: | http://dx.doi.org/10.1038/s41598-021-02060-1 |
Appears in Collections: | Medicine publications |
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hdl_133821.pdf | Published version | 2.84 MB | Adobe PDF | View/Open |
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