Dexamethasone inhibits the differentiation of rat tendon stem cells into tenocytes by targeting the scleraxis gene. Issue 152 (August 2015)

• Record Type: Journal Article
• Authors: Chen, Wan; Tang, Hong; Zhou, Mei; Hu, Chao; Zhang, Jiqiang; Tang, Kanglai
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 152(2015)
• Page Start: 16
• Page End: 24
• Publication Date: 2015-08
• Subjects: Dexamethasone -- Tendon stem cells -- Scleraxis -- Differentiation; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2015.04.010
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: We investigated the effect of Dex on differentiation of TSCs to tenocytes and the molecular mechanisms. Dex inhibits the differentiation of TSCs to tenocytes. Scx is downregulated in TSCs in vitro and in human tendon after treatment with Dex. ChIP showed that Dex promotes GR interacted with TGGAAGCC upstream of the Scx gene. Scx knockdown or overexpression affects the differentiation of TSCs to tenocytes. Abstract: Glucocorticoid-induced tendon rupture is very common in clinical practice, and the overall outcome of surgical suture repair is rather poor. The mechanism remains unclear, and effective treatments are still lacking. In the present study, we investigated the effect of dexamethasone on the differentiation of rat tendon stem cells (TSCs) to tenocytes and the underlying molecular mechanisms and found that dexamethasone inhibits the differentiation of TSCs to tenocytes by analyzing the development of long, spindle-shaped cells and detecting the expression of tenocyte markers type I collagen and tenomodulin (TNMD) at both the mRNA and protein levels. We also discovered that after treatment with dexamethasone, the scleraxis expression level is downregulated in vitro and in human specimen. Chromatin immunoprecipitation (ChIP)-PCR showed that dexamethasone promotes glucocorticoid receptor interacted with the TGGAAGCC sequence located between −734 and −726 base pairs (bp) upstream of the start codon of the scleraxis gene. Furthermore, TSCs were transfected with scleraxis knockdown or overexpression plasmids, and the results indicated that scleraxis plays a pivotal role in the differentiation of TSCs to tenocytes. In conclusion, dexamethasone inhibits the differentiation of TSCs to tenocytes by inhibiting the scleraxis gene.