Physiological concentrations of denosumab enhance osteogenic differentiation in human mesenchymal stem cells of the jaw bone.

Abstract

OBJECTIVE\nThe aim of this study was to evaluate the possible influence of denosumab and zoledronate on proliferation and osteogenic differentiation of alveolar bone stem cells.\n\n\nDESIGN\nMesenchymal stem cells (MSCs) and dental follicle cells (DFCs) were grown under osteogenic differentiation with concentrations from 0.25 μM to 10 μM (zoledronate) and to 20 μM (denosumab). Vitality was assessed after 7 days by CCK-8 Kit. Osteogenic differentiation was measured by alkaline phosphatase (ALP) assay and additionally by RT-qPCR of key enzymes COL1, RUNX2 and ALP.\n\n\nRESULTS\nMSCs expressed receptor activator of NF-κB (RANK), as requirement to interact with denosumab. DFCs did not express RANK. Denosumab significantly reduced proliferation and ALP activity of MSCs in high concentrations (10 μM and 20 μM). Growth of DFCs was not influenced at all by denosumab. Zoledronate reduced proliferation of DFCs in higher concentrations (5 μM and 10 μM) (p\u2009>\u20090.05). Physiological and medium concentrations of denosumab (0.25 μM, 1 μM 5μM) significantly enhanced ALP activity in MSCs and COL1, RUNX2 and ALP were upregulated. Zoledronate had no effect on ALP activity in DFCs.\n\n\nCONCLUSION\nOur evaluations suggest receptor and dose depending effects of denosumab in MSCs. High concentrations mediate toxic effects, whereas physiological and medium concentrations enhance osteogenic differentiation.