Imatinib promotes mineral formation in bone trephine explant cultures. (A) Posterior superior iliac spine bone trephine explant cultures were grown under osteoinductive conditions in the presence of various concentrations of imatinib for 4 weeks. Mineralized matrix was solubilized in 0.6 M HCl and the concentration of calcium per 105 cells quantified as previously described.20 A dose-dependent increase in mineral formation was observed in the presence of imatinib. Mean values are shown; error bars represent the standard error of triplicate measurements. *P ≤ .05. (B) To examine whether the mechanism by which imatinib increased mineral formation was through inhibition of the PDGF receptor, mineralization assays were performed in the presence of exogenous PDGF-BB (10 ng/mL). The addition of PDGF-BB to control cultures (■) decreased mineral formation, which was overcome by the addition of 3 μM imatinib (□). Mean values are shown; error bars represent the standard error of triplicate measurements. (C) In addition to promoting mineral formation, imatinib induced adipocyte formation in osteogenic cultures. Lipid droplets are stained with Oil Red O and cells counterstained with hematoxylin. Original magnification 40×. UT denotes untreated cells; IM, imatinib-treated cells. Images acquired as detailed in the Figure 1 legend.
