KLF2 reduces dexamethasone-induced injury to growth plate chondrocytes by inhibiting the Runx2-mediated PI3K/AKT and ERK signalling pathways

Abstract

Dexamethasone (Dex) is a type of glucocorticoid drug. Long term use can induce growth plate chondrocytes (GPCs) apoptosis, impair differentiation, and inhibit cell proliferation and bone growth. It has been reported that Krüppel-like factor 2 (KLF2) inhibits osteoblast damage induced by Dex, but the role in Dex-induced GPCs remains unclear. Dex was used to construct a model of growth plate injury in vitro. CCK-8 and TUNEL kits were used to determine cell viability and apoptosis. A model of growth plate injury was established by intraperitoneal injection of Dex. Immunohistochemistry was used to investigate the expression of KLF2 in rats. The results showed that KLF2 expression of rat tibial GPCs was down-regulated after Dex stimulation. Overexpression of KLF2 promoted cell viability and cell cycle, while inhibited apoptosis of growth plate Dex-induced chondrocytes. Moreover, KLF2 inhibited Runx2-mediated PI3K/AKT and ERK signalling pathways. And PI3K/AKT and ERK signalling pathways, which were involved in the regulation of KLF2 on GPCs. Further studies showed that KLF2 alleviated growth plate injury in vivo. In conclusion, our study found that KLF2 promoted proliferation and inhibited apoptosis of Dex-induced GPCs by targeting the Runx2-mediated PI3K/AKT and ERK signalling pathways.

Keywords:

• KLF2
• Runx2
• growth plate chondrocytes
• PI3K/AKT pathways
• apoptosis

Authors’ contributions

Xiaowei Wang was involved in study design, implementation of the experiments and data analysis. Yulong Ma and Tao Peng were involved in data analysis and interpretation, and drafting of the manuscript. Xudong Yao and Chaonan Sun were involved in data analysis and revision of the manuscript.

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

The authors declare that they have no competing interests.

Funding

The author(s) reported there is no funding associated with the work featured in this article.