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Article

Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via SOX9 and PPARG, but Not RUNX2

1
AO Research Institute Davos, 7270 Davos Platz, Switzerland
2
Laboratory of applied microbiology (LMA), Department of Environment, Constructions and Design (DACD), University of Applied Sciences of Southern Switzerland (SUPSI), 6500 Bellinzona, Switzerland
3
Swiss Institute of Bioinformatics, Quartier Sorge—Batiment Genopode, 1015 Lausanne, Switzerland
4
Dalle Molle Institute for Artificial Intelligence (IDSIA), University of Italian Switzerland (USI), 6928 Manno, Switzerland
5
University of Applied Science and Art of Southern Switzerland (SUPSI), 6928 Manno, Switzerland
6
Department of Orthopedics and Trauma Surgery, Medical Center—Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Giacomina Brunetti
Int. J. Mol. Sci. 2021, 22(9), 4785; https://doi.org/10.3390/ijms22094785
Received: 19 March 2021 / Revised: 24 April 2021 / Accepted: 28 April 2021 / Published: 30 April 2021
Despite the huge body of research on osteogenic differentiation and bone tissue engineering, the translation potential of in vitro results still does not match the effort employed. One reason might be that the protocols used for in vitro research have inherent pitfalls. The synthetic glucocorticoid dexamethasone is commonly used in protocols for trilineage differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). However, in the case of osteogenic commitment, dexamethasone has the main pitfall of inhibiting terminal osteoblast differentiation, and its pro-adipogenic effect is well known. In this work, we aimed to clarify the role of dexamethasone in the osteogenesis of hBMSCs, with a particular focus on off-target differentiation. The results showed that dexamethasone does induce osteogenic differentiation by inhibiting SOX9 expression, but not directly through RUNX2 upregulation as it is commonly thought. Rather, PPARG is concomitantly and strongly upregulated, leading to the formation of adipocyte-like cells within osteogenic cultures. Limiting the exposure to dexamethasone to the first week of differentiation did not affect the mineralization potential. Gene expression levels of RUNX2, SOX9, and PPARG were simulated using approximate Bayesian computation based on a simplified theoretical model, which was able to reproduce the observed experimental trends but with a different range of responses, indicating that other factors should be integrated to fully understand how dexamethasone influences cell fate. In summary, this work provides evidence that current in vitro differentiation protocols based on dexamethasone do not represent a good model, and further research is warranted in this field. View Full-Text
Keywords: Osteogenesis; glucocorticoids; transcription factors; MSC; gene expression; approximate Bayesian computation (ABC) Osteogenesis; glucocorticoids; transcription factors; MSC; gene expression; approximate Bayesian computation (ABC)
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MDPI and ACS Style

Della Bella, E.; Buetti-Dinh, A.; Licandro, G.; Ahmad, P.; Basoli, V.; Alini, M.; Stoddart, M.J. Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via SOX9 and PPARG, but Not RUNX2. Int. J. Mol. Sci. 2021, 22, 4785. https://doi.org/10.3390/ijms22094785

AMA Style

Della Bella E, Buetti-Dinh A, Licandro G, Ahmad P, Basoli V, Alini M, Stoddart MJ. Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via SOX9 and PPARG, but Not RUNX2. International Journal of Molecular Sciences. 2021; 22(9):4785. https://doi.org/10.3390/ijms22094785

Chicago/Turabian Style

Della Bella, Elena, Antoine Buetti-Dinh, Ginevra Licandro, Paras Ahmad, Valentina Basoli, Mauro Alini, and Martin J. Stoddart. 2021. "Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via SOX9 and PPARG, but Not RUNX2" International Journal of Molecular Sciences 22, no. 9: 4785. https://doi.org/10.3390/ijms22094785

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