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Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist
In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient “chondrocytes” in the growth plate. As hypertrophy would result in ossification, this fact limits their use in cartilage tissue engineering applications. Dur...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073129/ https://www.ncbi.nlm.nih.gov/pubmed/32093330 http://dx.doi.org/10.3390/ijms21041444 |
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author | Riedl, Moritz Witzmann, Christina Koch, Matthias Lang, Siegmund Kerschbaum, Maximilian Baumann, Florian Krutsch, Werner Docheva, Denitsa Alt, Volker Pfeifer, Christian |
author_facet | Riedl, Moritz Witzmann, Christina Koch, Matthias Lang, Siegmund Kerschbaum, Maximilian Baumann, Florian Krutsch, Werner Docheva, Denitsa Alt, Volker Pfeifer, Christian |
author_sort | Riedl, Moritz |
collection | PubMed |
description | In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient “chondrocytes” in the growth plate. As hypertrophy would result in ossification, this fact limits their use in cartilage tissue engineering applications. During limb development, retinoic acid receptor (RAR) signaling exerts an important influence on cell fate of mesenchymal progenitors. While retinoids foster hypertrophy, suppression of RAR signaling seems to be required for chondrogenic differentiation. Therefore, we hypothesized that treatment of chondrogenically differentiating hMSCs with the RAR inverse agonist, BMS204,493 (further named BMS), would attenuate hypertrophy. We induced hypertrophy in chondrogenic precultured MSC pellets by the addition of bone morphogenetic protein 4. Direct activation of the RAR pathway by application of the physiological RAR agonist retinoic acid (RA) further enhanced the hypertrophic phenotype. However, BMS treatment reduced hypertrophic conversion in hMSCs, shown by decreased cell size, number of hypertrophic cells, and collagen type X deposition in histological analyses. BMS effects were dependent on the time point of application and strongest after early treatment during chondrogenic precultivation. The possibility of modifing hypertrophic cartilage via attenuation of RAR signaling by BMS could be helpful in producing stable engineered tissue for cartilage regeneration. |
format | Online Article Text |
id | pubmed-7073129 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70731292020-03-19 Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist Riedl, Moritz Witzmann, Christina Koch, Matthias Lang, Siegmund Kerschbaum, Maximilian Baumann, Florian Krutsch, Werner Docheva, Denitsa Alt, Volker Pfeifer, Christian Int J Mol Sci Article In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient “chondrocytes” in the growth plate. As hypertrophy would result in ossification, this fact limits their use in cartilage tissue engineering applications. During limb development, retinoic acid receptor (RAR) signaling exerts an important influence on cell fate of mesenchymal progenitors. While retinoids foster hypertrophy, suppression of RAR signaling seems to be required for chondrogenic differentiation. Therefore, we hypothesized that treatment of chondrogenically differentiating hMSCs with the RAR inverse agonist, BMS204,493 (further named BMS), would attenuate hypertrophy. We induced hypertrophy in chondrogenic precultured MSC pellets by the addition of bone morphogenetic protein 4. Direct activation of the RAR pathway by application of the physiological RAR agonist retinoic acid (RA) further enhanced the hypertrophic phenotype. However, BMS treatment reduced hypertrophic conversion in hMSCs, shown by decreased cell size, number of hypertrophic cells, and collagen type X deposition in histological analyses. BMS effects were dependent on the time point of application and strongest after early treatment during chondrogenic precultivation. The possibility of modifing hypertrophic cartilage via attenuation of RAR signaling by BMS could be helpful in producing stable engineered tissue for cartilage regeneration. MDPI 2020-02-20 /pmc/articles/PMC7073129/ /pubmed/32093330 http://dx.doi.org/10.3390/ijms21041444 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Riedl, Moritz Witzmann, Christina Koch, Matthias Lang, Siegmund Kerschbaum, Maximilian Baumann, Florian Krutsch, Werner Docheva, Denitsa Alt, Volker Pfeifer, Christian Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist |
title | Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist |
title_full | Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist |
title_fullStr | Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist |
title_full_unstemmed | Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist |
title_short | Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist |
title_sort | attenuation of hypertrophy in human mscs via treatment with a retinoic acid receptor inverse agonist |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073129/ https://www.ncbi.nlm.nih.gov/pubmed/32093330 http://dx.doi.org/10.3390/ijms21041444 |
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