Abstract: Objective  To explore the influence of insulin receptor substrate 1(IRS-1)/transcriptional coactivator with PDZ-binding motif(TAZ) signaling on the osteogenic differentiation of bone marrow derived mesenchymal stem cells(BMSCs). 
Methods  In vivo, the bone mass of rat femurs in control group, sham group and ovariectomy(OVX) group was analyzed by micro-computed tomography(μCT) and the IRS-1 expression in rat femurs was analyzed by immunofluorescence assay. In vitro, the plasmid transfection was used to change the IRS-1 and TAZ expression in BMSCs, the alizarin red staining and western blot was used to analyze the calcium nodules and the expression of the osteogenic differentiation related proteins, respectively. 
Results  The bone mass and the IRS-1 expression in rat femurs was significantly reduced in OVX group. High expression of IRS-1 in BMSCs increased the expression of TAZ, runt related transcription factor 2(RUNX2) and osteocalcin(OCN) proteins, which promoted the osteogenic differentiation of BMSCs. Knockout of IRS-1 or TAZ inhibited the osteogenic differentiation of BMSCs. 
Conclusion  IRS-1 increased the TAZ expression, which promoted the osteogenic differentiation of BMSCs. IRS-1/TAZ signaling in stem cells might be a new target to treat diabetic osteoporosis. 

Key words: osteoporosis, bone marrow derived mesenchymal stem cell, insulin receptor substrate 1