Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, People's Republic of China.
Int J Nanomedicine. 2020 Apr 14;15:2419-2435. doi: 10.2147/IJN.S245174. eCollection 2020.
In recent years, nanomaterials have been increasingly developed and applied in the field of bone tissue engineering. However, there are few studies on the induction of bone regeneration by tantalum nanoparticles (Ta NPs) and no reports on the effects of Ta NPs on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanisms. The main purpose of this study was to investigate the effects of Ta NPs on bone regeneration and BMSC osteogenic differentiation and the underlying mechanisms.
The effects of Ta NPs on bone regeneration were evaluated in an animal experiment, and the effects of Ta NPs on osteogenic differentiation of BMSCs and the underlying mechanisms were evaluated in cell experiments. In the animal experiment, hematoxylin-eosin (HE) staining and hard-tissue section analysis showed that Ta NPs promoted bone regeneration, and immunohistochemistry revealed elevated expression of BMP2 and Smad4 in cells cultured with Ta NPs.
The results of the cell experiments showed that Ta NPs promoted BMSC proliferation, alkaline phosphatase (ALP) activity, BMP2 secretion and extracellular matrix (ECM) mineralization, and the expression of related osteogenic genes and proteins (especially BMP2, Smad4 and Runx2) was upregulated under culture with Ta NPs. Smad4 expression, ALP activity, ECM mineralization, and osteogenesis-related gene and protein expression decreased after inhibiting Smad4.
These data suggest that Ta NPs have an osteogenic effect and induce bone regeneration by activating the BMP2/Smad4/Runx2 signaling pathway, which in turn causes BMSCs to undergo osteogenic differentiation. This study provides insight into the molecular mechanisms underlying the effects of Ta NPs in bone regeneration.
近年来，纳米材料在骨组织工程领域得到了越来越多的开发和应用。然而，关于钽纳米粒子（Ta NPs）诱导骨再生的研究较少，也没有关于 Ta NPs 对骨髓间充质干细胞（BMSCs）成骨分化的影响及其潜在机制的报道。本研究的主要目的是探讨 Ta NPs 对骨再生和 BMSC 成骨分化的影响及其潜在机制。
在动物实验中评估 Ta NPs 对骨再生的影响，在细胞实验中评估 Ta NPs 对 BMSCs 成骨分化的影响及其潜在机制。在动物实验中，苏木精-伊红（HE）染色和硬组织切片分析表明 Ta NPs 促进骨再生，免疫组织化学显示 Ta NPs 培养的细胞中 BMP2 和 Smad4 的表达升高。
细胞实验结果表明，Ta NPs 促进 BMSC 增殖、碱性磷酸酶（ALP）活性、BMP2 分泌和细胞外基质（ECM）矿化，并且 Ta NPs 培养上调相关成骨基因和蛋白（尤其是 BMP2、Smad4 和 Runx2）的表达。抑制 Smad4 后，Smad4 表达、ALP 活性、ECM 矿化和成骨相关基因和蛋白表达降低。
这些数据表明，Ta NPs 具有成骨作用，并通过激活 BMP2/Smad4/Runx2 信号通路诱导骨再生，从而促使 BMSCs 发生成骨分化。本研究为 Ta NPs 在骨再生中的作用的分子机制提供了新的见解。
