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

Na Wang,Ziyi Li,Yukun Li,Peng Xue

doi:10.1242/bio.036194

Abstract

ABSTRACTWhether 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.

Highlights

Bone tissue could be continuously regenerated, but it often fails when the healing capacity is compromised (Lupsa and Insogna, 2015)
Gene expression of insulin receptor substrate 1 (IRS-1) was associated with Transcriptional co-activator with PDZbinding motif (TAZ) during osteogenic differentiation of passage 3 Bone marrow mesenchymal stem cells (BMSCs) Passage 3 BMSCs were positive for cell lineage markers such as CD29 (100%) and CD90 (96.8%), and negative for CD34 (0.6%) and CD45 (1.6%) (Fig. 1A)
The real-time RT-PCR results showed that Insulin receptor substrate (IRS)-1 expression was increased in a time-dependent manner during the process of the BMSCs’ osteogenic differentiation (Fig. 1F)

Summary

Introduction

Bone tissue could be continuously regenerated, but it often fails when the healing capacity is compromised (Lupsa and Insogna, 2015). Many clinical conditions, such as osteoporosis or diabetes, make bone remodeling difficult. We have discovered that exogenous stimuli, such as insulin/ IGF-1, could increase TAZ expression to promote osteogenic differentiation in BMSCs (Xue et al, 2013). It is of interest whether or not TAZ plays an important role in insulin/IGF-1 pathways during the BMSCs’ osteoblastogenesis

Methods

Results

Conclusion