Comparative Chondrogenic Efficacy of Dexamethasone Versus Fluocinolone Acetonide Under Varying Insulin and Glucose Concentrations in Defined Media
- 1Department of Chemical and Biomolecular Engineering, Center for Modular Manufacturing of Structural Tissues, Case Western Reserve University, 2102 Adelbert Road, 142 A.W. Smith Building, Cleveland, OH 44106, USA
- 2Department of Biology, Center for Modular Manufacturing of Structural Tissues, Case Western Reserve University, Cleveland, OH 44106, USA
Abstract
Chondrogenic differentiation of human mesenchymal stem cells (hMSCs) is significantly influenced by the biochemical composition of the culture microenvironment, including corticosteroid type, glucose availability, and insulin supplementation. Although dexamethasone (DXM) remains the standard glucocorticoid for chondrogenic induction, hypertrophic differentiation remains an important limitation of hMSC-based cartilage tissue engineering. Fluocinolone acetonide (FA) has shown promise in potentiating chondrogenesis with TGF-β3, but its behavior under varying metabolic conditions remains unclear. This study used a three-factor design to evaluate the effects of corticosteroid type (DXM vs. FA), glucose concentration (1 to 4.5 g/L), and insulin level (0 to 4.3 µM) on hMSC aggregate chondrogenesis over 21 days. Outcomes were assessed via biochemical assays, histology, and immunohistochemistry. FA-treated aggregates generally exhibited a smaller, more compact morphology than DXM-treated aggregates. Selected FA conditions, particularly at higher insulin concentrations, showed stronger Safranin O and collagen II staining with limited collagen X staining. DXM-treated aggregates were generally larger and more irregular and showed collagen X staining under selected low- and high-glucose conditions. DXM-treated aggregates also consumed more glucose and produced more lactate than FA-treated aggregates. These findings indicate that FA and DXM produce distinct chondrogenic and metabolic responses and suggest that FA may be used as an alternative corticosteroid for cartilage tissue engineering. The results also highlight the importance of considering both insulin and glucose concentrations when formulating defined chondrogenic media.
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BibTeX
@article{chen2026comparative,
title = {{Comparative Chondrogenic Efficacy of Dexamethasone Versus Fluocinolone Acetonide Under Varying Insulin and Glucose Concentrations in Defined Media}},
author = {Bo-An Chen and Nima Firouzi and Rodrigo A. Somoza and Harihara Baskaran},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212034},
url = {https://www.mdpi.com/2073-4409/15/21/2034},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative Chondrogenic Efficacy of Dexamethasone Versus Fluocinolone Acetonide Under Varying Insulin and Glucose Concentrations in Defined Media
AU - Bo-An Chen
AU - Nima Firouzi
AU - Rodrigo A. Somoza
AU - Harihara Baskaran
PY - 2026
DA - 2026/11/07
JO - Cells
DO - 10.3390/cells15212034
UR - https://www.mdpi.com/2073-4409/15/21/2034
AB - Chondrogenic differentiation of human mesenchymal stem cells (hMSCs) is significantly influenced by the biochemical composition of the culture microenvironment, including corticosteroid type, glucose availability, and insulin supplementation. Although dexamethasone (DXM) remains the standard glucocorticoid for chondrogenic induction, hypertrophic differentiation remains an important limitation of hMSC-based cartilage tissue engineering. Fluocinolone acetonide (FA) has shown promise in potentiating chondrogenesis with TGF-β3, but its behavior under varying metabolic conditions remains unclear. This study used a three-factor design to evaluate the effects of corticosteroid type (DXM vs. FA), glucose concentration (1 to 4.5 g/L), and insulin level (0 to 4.3 µM) on hMSC aggregate chondrogenesis over 21 days. Outcomes were assessed via biochemical assays, histology, and immunohistochemistry. FA-treated aggregates generally exhibited a smaller, more compact morphology than DXM-treated aggregates. Selected FA conditions, particularly at higher insulin concentrations, showed stronger Safranin O and collagen II staining with limited collagen X staining. DXM-treated aggregates were generally larger and more irregular and showed collagen X staining under selected low- and high-glucose conditions. DXM-treated aggregates also consumed more glucose and produced more lactate than FA-treated aggregates. These findings indicate that FA and DXM produce distinct chondrogenic and metabolic responses and suggest that FA may be used as an alternative corticosteroid for cartilage tissue engineering. The results also highlight the importance of considering both insulin and glucose concentrations when formulating defined chondrogenic media.
SN - 2073-4409
ER -