The Influence of Zoledronic Acid on the Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells and Tibial Fracture in Rats via Phosphatidylinositol-3-Kinase/AKT Pathway

Abstract

Fracture healing is an extremely complex physiological process, involving a sequence of crucial mechanisms. Whether zoledronic acid (ZA) affects proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and tibial fractures still remains unknown. We performed construction of the tibial fracture model in rats and analyzed the impact of ZA and ZA+LY294002 on fracture healing in rats. Test of the influence of ZA and ZA+LY294002 on crucial osteogenic genes alkaline phosphatase (ALP), RUNX2, OCN and OPN was performed. Examination of the influence of suppressing the PI3K/AKT pathway on the proliferation with bone differentiation of ZA. Results showed ZA distinctly accelerated the proliferation and ALP activity of BMSC cells, BMP2, RUNX2, OCN, OPN and the activation of the PI3K/AKT pathway. Repression of PI3K/AKT pathway suppressed the proliferation and osteogenic differentiation action of ZA. ZA boosted tibial fracture healing in rats via activating the PI3K/AKT pathway. ZA facilitates the proliferation with osteogenic differentiation of BMSC cells and tibial fracture healing in rats via activating the PI3K/AKT pathway.