Effects of IL-1 Receptor-Associated Kinase-4 Gene Silencing on Human Osteoblast-Like Cells

Abstract

The aim of this study is to identify the effects of interleukin-1 receptor-associated kinase-4 (IRAK-4) gene silencing on human osteoblast-like cells. The siRNA sequences of the target gene, IRAK-4, were constructed and transferred into MG63 cells (control group = MG63 cells; SC group = MG63 cells transfected with scrambled IRAK-4 siRNA; KD group = MG63 cells transfected with 75 nM IRAK-4 siRNA). The morphological changes, cell growth, cell-cycle progression, apoptosis, and the expression of various cytokines and proteins were compared. Compared with the control and SC groups, IRAK-4 gene silencing in MG63 cells caused morphological changes, inhibited growth, altered the cell-cycle distribution, increased apoptosis (p < 0.05), decreased bone alkaline phosphatase and osteocalcin levels (p < 0.05), and decreased protein expression of Bcl-2/Bax and Bcl-2, p-JNK1/2, p-ERK1/2, and p-p38MAPK (p < 0.05). The results indicated that IRAK-4 gene silencing in MG63 cells inhibited cell proliferation and function and increase apoptosis, which may be related to the decreased Bcl-2/Bax ratio and inhibition of the protein expression of various components of the mitogen-activated protein kinase pathways. The results of this study may help improve the understanding of the relationship between IRAK-4 and osteoblast-like cells and the interactions between various cytokines in the periprosthetic inflammatory environment.

• human osteoblast-like cells
• IRAK-4
• cell function
• siRNA
• MG63 cells

Acknowledgments

This study was supported by the National Basic Research Program (Grant No. 2012CB619105), the Key Program of National Natural Science Foundation of China-Guangdong Joint Funding (Grant No. u0732001), the International S&T Cooperation Network Project of Danish Council for Strategic Research for Individualized Musculoskeletal Regeneration and Reconstruction Network (Grant No. 2101-07-0120), the Project of Chinese-German Junior Research Group on Biotechnology (Grant No. 2009004), and the China Postdoctoral Science Foundation (Grant No. 20100480810).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.