College of Biomedical Engineering, Sichuan University, No. 24 South Section 1, Yihuan Road, Chengdu, Sichuan 610065, P. R. China.
ACS Appl Bio Mater. 2023 Sep 18;6(9):3863-3874. doi: 10.1021/acsabm.3c00486. Epub 2023 Aug 30.
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.
五价钒[V(V)]已被研究为生物活性离子，以改善骨缺损修复；然而，其成骨促进机制迄今尚未完全了解。在这项研究中，制备了一种掺杂 V 的介孔生物活性玻璃（V-MBG），并研究了其对大鼠骨髓间充质干细胞（rBMSCs）成骨分化的影响及其潜在的信号通路。理化特性表明，V 的掺入略微降低了比表面积并增加了介孔孔径，而 V-MBG 的丰富介孔有利于 V(V)离子以及钙、硅和磷离子的持续溶解。细胞增殖结果表明，与对照组和相同稀释率 MBG 提取物相比，高稀释率（>16）V-MBG 提取物明显促进 rBMSCs 的增殖。与相同稀释率 MBG 提取物相比，稀释的 V-MBG 提取物在第 7 天明显促进碱性磷酸酶（ALP）和骨钙素（OCN）蛋白的分泌，但对 runt 相关转录因子 2（RUNX2）和血管内皮生长因子（VEGF）蛋白的合成刺激作用不明显。深入研究表明，与相同稀释率 MBG 提取物相比，稀释的 V-MBG 提取物显著上调了 WNT/β-连环蛋白通路直接靶基因的表达，包括 WNT3a、β-连环蛋白和 AXIN2 基因，表明释放的 V(V)离子可能通过 WNT/β-连环蛋白信号通路促进 rBMSCs 的成骨分化。
