Pamidronate Disodium Leads to Bone Necrosis via Suppression of Wnt/β-Catenin Signaling in Human Bone Marrow Mesenchymal Stem Cells In Vitro

Purpose Pamidronate disodium–associated bone necrosis is poorly understood at the cellular and molecular levels. This study proposes a pathway leading to the pamidronate disodium–mediated inhibition of osteogenic differentiation of human bone marrow mesenchymal stem cells (BMMSCs) derived from the mandible in vitro. Materials and Methods Primary human BMMSCs were isolated from the mandible and marrow tissue. A proliferation assay was performed to determine the experimental concentration of pamidronate disodium. Alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S (ARS) staining were assessed after treatment with pamidronate disodium (0, 0.1, 0.5, 1, 5, 10 μg/mL). Quantitative real-time polymerase chain reaction and western blotting specific for Wnt and β-catenin signaling genes or proteins were performed after treatment with pamidronate disodium 0.5 μg/mL. Wnt3a was used to observe the osteogenic differentiation of BMMSCs during treatment with pamidronate disodium 0.5 μg/mL. Results As expected, pamidronate disodium 1, 5, and 10 μg/ml were unfavorable for BMMSC growth ( P