Dexamethasone Interferes with the Chondrogenic Differentiation and Upregulates the Expression of Genes in Integrin and Notch Signaling Pathways

초록

Glucocorticoids including Dexamethasone (DEX) are often used to control imflammatory responses but whose long term use at high dose can impair the bone growth. However, its underlying mechanisms associated with the osteopathogenesis remains poorly characterized. In differentiation media containing ITS1 and/or BMP4, ATDC5 chondroprogenitor cells go through early chondrogenic differentiation process to exhibit cellular condensation and nodule formation. In this study employing Alcian blue staining, mouse Illumina microarray and RT-PCR techniques, we attempted (1) to investigate whether DEX can influence on early chondrogenic step, and (2) to characterize differential expression of genes that may contribute to the side effect. Our data show that DEX could interfere with early condensation process and induce the expression of genes belonging to integrin and notch signaling pathways. Based on recent reports demonstrating the cooperation of both signaling pathways in cell adhesion, we propose that DEX may modulate the differentiation of chondroprogenitor cells by influencing Notch and integrin signaling activities.

키워드