Vanadium-Doped Mesoporous Bioactive Glass Promotes Osteogenic Differentiation of rBMSCs via the WNT/β-Catenin Signaling Pathway.

Abstract

Pentavalent vanadium [V(V)] has been studied as bioactive ions to improve the bone defect repair; however, its osteogenic promotion mechanism is still not fully understood so far. In this study, a V-doped mesoporous bioactive glass (V-MBG) was prepared, and its effects on osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and potential signaling pathways were investigated. The physicochemical characterization revealed that the incorporation of V slightly reduced the specific surface area and increased the mesoporous pore size, and the abundant mesopores of V-MBG were beneficial to the sustained dissolution of V(V) ions as well as calcium, silicon, and phosphorus ions. Cell proliferation results indicated that the high dilution ratio (>16) V-MBG extract markedly promoted the proliferation of rBMSCs compared with the control group and the same dilution ratio MBG extract. Compared with the same dilution ratio MBG extract, diluted V-MBG extracts markedly promoted the secretion of alkaline phosphatase (ALP) and osteocalcin (OCN) protein at day 7 but insignificantly stimulated the runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF) protein synthesis. In depth, the diluted V-MBG extracts remarkably up-regulated the expression of WNT/β-catenin pathway direct target genes, including WNT3a, β-catenin, and AXIN2 genes in contrast to the same dilution ratio MBG extracts, suggesting that the released V(V) ions might promote osteogenic differentiation of rBMSCs via the WNT/β-catenin signaling pathway.