Molecular and cellular outcomes of quercetin actions on healthy and tumor osteoblasts

There is a global trend in the use of natural bioactive compounds to complement conventional therapies in bone diseases. In this work, we studied the effects of the phytoestrogen quercetin (QUE) in healthy and tumor osteoblasts. We found that QUE (1 mu M, 48 h) significantly increased the cell number and the viability of healthy human osteoblasts (hFOB cells) determined by a trypan blue and a MTS assay, respectively, among other concentrations tested. In addition, wound healing and cellular adhesion assays also demonstrated that 1 mu M of QUE significantly stimulated both parameters in osteoblasts. Moreover, osteoblast differentiation was also triggered by QUE in an osteogenic medium by measuring alkaline phosphatase activity, calcium deposition, and collagen levels. Herein, a concentration of 0.01 mu M of QUE showed an increment in these differentiation markers and an activation of AKT/GSK3 beta/beta-catenin pathway, determined by a Western blot analysis. In addition, immunocytochemistry and subcellular fraction studies indicated an increase of beta-catenin localization in the plasma membrane after QUE treatment. Otherwise, QUE (20-100 mu M) decreased the cell number and the viability in tumor osteo-blasts (ROS 17/2.8 cells) after 48 h. Furthermore, QUE (100 mu M) decreased AKT(Ser473) and the pro-apoptotic protein BAD(Ser136) phosphorylation. In addition, the ERK1/2 phosphorylation increased leading to osteosarcoma cell death since pre-treatment with the MEK inhibitor PD98059 had reverted QUE effect. Altogether, these results indicate that low concentrations of QUE stimulate osteoblasto-genesis but have no effect on the growth of tumor osteoblast cells, for which only high concentrations are efficient. (c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

This study investigated the effects of phytoestrogen quercetin on healthy and tumor osteoblasts. The results showed that low concentrations of quercetin stimulated proliferation, viability, and differentiation of healthy osteoblasts, while high concentrations were effective in inhibiting the growth of tumor osteoblasts.