New pathway of icariin-induced MSC osteogenesis: transcriptional activation of TAZ/Runx2 by PI3K/Akt

Abstract Icariin has been demonstrated to stimulate mesenchymal stem cell (MSC) osteogensis and activate several signals, such as PI3K/Akt, but how the osteogenesis was sequentially mediated is unclear. Runx2 is one of the osteogenic regulators in MSC and is regulated by the TAZ gene. The purpose of this study was to investigate whether icariin-activated PI3K/Akt crosstalked with the TAZ-Runx2 pathway to regulate MSC osteogenesis. Adipose-derived MSCs were treated with icariin alone, together with TAZ silencing or PI3K/Akt inhibitor. Normal MSCs were used as a control. The activation of PI3K/Akt, expression of TAZ and downstream expression of Runx2 were analyzed. Induction of MSC osteogenesis under different treatments was detected. The results demonstrated that icariin treatment significantly activated PI3K/Akt and TAZ expression, as well as the downstream Runx2 expression. When activation of PI3K/Akt by icariin was inhibited by LY294002, upregulated TAZ expression was reversed, as well as the downstream expression of Runx2. Consequently, with the osteogenic counteracting effects of icariin on MSCs, inhibition of TAZ upregulation by siRNA did not significantly influence PI3K/ Akt activation in icariin-treated MSCs, but icariin-induced upregulation of Runx2 and osteogenic differentiation in MSCs was counteracted. It could be concluded from these findings that icariin treatment activated PI3K/Akt and further mediated the transcriptional activation of the TAZ/Runx2 pathway to induce osteogenic differentiation of MSCs.