IRS-1 increases TAZ expression and promotes osteogenic differentiation in rat bone marrow mesenchymal stem cells

ABSTRACT

Whether insulin receptor substrate 1 (IRS-1) inhibits or promotes the osteogenic proliferation and differentiation in vitro remains controversial. Transcriptional co-activator with PDZ-binding motif (TAZ) plays a vital role in the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), and strongly activates the expression of the osteogenic differentiation markers. In this study, we found that IRS-1 and TAZ followed similar increasing expression patterns at the early stage of osteogenic differentiation. Knocking down IRS-1 decreased the TAZ, RUNX2 and OCN expression, and overexpressing IRS induced the upregulation of the TAZ, RUNX2 and OCN expression. Furthermore, our results showed that it was LY294002 (the PI3K-Akt inhibitor), other than UO126 (the MEK-ERK inhibitor), that inhibited the IRS-1 induced upregulation of TAZ expression. Additionally, SiTAZ blocked the cell proliferation in G1 during the osteogenic differentiation of BMSCs. Taken together, we provided evidence to demonstrate that IRS-1 gene modification facilitates the osteogenic differentiation of rat BMSCs by increasing TAZ expression through the PI3K-Akt signaling pathway.

This article has an associated First Person interview with the first author of the paper .

Abstract

Summary: Stem cell therapy has become a promising approach for bone tissue engineering. Our study reveals that IRS-1 gene modification of stem cells upregulates TAZ expression and osteogenesis.