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

Autor: Prideaux M; Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA., Wright CS; Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA.; Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, 46202, USA., Noonan ML; Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA.; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, 46202, USA., Yi X; Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, 46202, USA., Clinkenbeard EL; Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA.; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, 46202, USA., Mevel E; Department of Anatomy, Cell Biology, and Physiology, Indiana University, Indianapolis, IN, 46202, USA., Wheeler JA; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, 46202, USA., Byers S; Centre for Orthopaedic and Trauma Research, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia., Wijenayaka AR; Centre for Orthopaedic and Trauma Research, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia., Gronthos S; Mesenchymal Stem Cell Laboratory, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia.; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia., Sankar U; Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA.; Department of Anatomy, Cell Biology, and Physiology, Indiana University, Indianapolis, IN, 46202, USA., White KE; Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA.; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, 46202, USA.; Centre for Orthopaedic and Trauma Research, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia., Atkins GJ; Centre for Orthopaedic and Trauma Research, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia., Thompson WR; Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA. wrthomps@uab.edu.; Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, 46202, USA. wrthomps@uab.edu.; Department of Anatomy, Cell Biology, and Physiology, Indiana University, Indianapolis, IN, 46202, USA. wrthomps@uab.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Nov 19; Vol. 11 (1), pp. 22593. Date of Electronic Publication: 2021 Nov 19.
DOI: 10.1038/s41598-021-02060-1
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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