Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou, 510515, China.
J Nanobiotechnology. 2020 Aug 31;18(1):119. doi: 10.1186/s12951-020-00663-w.
A novel bioactive inorganic material containing silicon, calcium and oxygen, calcium silicate (CaSiO, CS) with a CaO-SiO ingredient, has been identified as a potential candidate for artificial bone. Autophagy has an essential function in adult tissue homoeostasis and tumorigenesis. However, little is known about whether silicate nanoparticles (CS NPs) promote osteoblastic differentiation by inducing autophagy. Here we investigated the effects of CS NPs on bone marrow mesenchymal stem cell differentiation (BMSCs) in osteoblasts. Furthermore, we identified the osteogenic gene and protein expression in BMSCs treated with CS NPs. We found that autophagy is important for the ability of CS NPs to induce osteoblastic differentiation of BMSCs. Our results showed that treatment with CS NPs upregulated the expression of BMP2, UNX2, and OSX in BMSCs, and significantly promoted the expression of LC3 and Beclin, while P62 (an autophagy substrate) was downregulated. CS NP treatment could also enhance Alizarin red S dye (ARS), although alkaline phosphatase (ALP) activity was not significantly changed. However, all these effects could be partially reversed by 3-MA. We then detected potential signaling pathways involved in this biological effect and found that CS NPs could activate autophagy by suppressing mTOR and facilitating ULK1 expression. Autophagy further activated β-catenin expression and promoted osteogenic differentiation. In conclusion, CS NPs promote bone formation and osteogenic differentiation in BMSCs by activating autophagy. They achieve this effect by activating mTOR/ULK1, inducing autophagy, and subsequently triggering the WNT/β-catenin pathway to boost the differentiation and biomineralization of osteoblasts.
一种新型的含硅、钙和氧的生物活性无机材料，硅酸钙（CaSiO 3 ，CS），具有 CaO-SiO 成分，已被确定为人工骨的潜在候选材料。自噬在成人组织稳态和肿瘤发生中具有重要功能。然而，人们对硅酸盐纳米颗粒（CS NPs）是否通过诱导自噬促进成骨细胞分化知之甚少。在这里，我们研究了 CS NPs 对成骨细胞中骨髓间充质干细胞分化（BMSCs）的影响。此外，我们鉴定了 CS NPs 处理的 BMSCs 中的成骨基因和蛋白表达。我们发现自噬对于 CS NPs 诱导 BMSCs 成骨分化的能力很重要。我们的结果表明，CS NPs 处理可上调 BMSCs 中 BMP2、UNX2 和 OSX 的表达，并显著促进 LC3 和 Beclin 的表达，同时下调 P62（自噬底物）。CS NP 处理还可以增强茜素红 S 染料（ARS）的染色，尽管碱性磷酸酶（ALP）活性没有明显改变。然而，所有这些作用都可以被 3-MA 部分逆转。然后，我们检测了涉及这种生物学效应的潜在信号通路，发现 CS NPs 可以通过抑制 mTOR 并促进 ULK1 表达来激活自噬。自噬进一步激活 β-catenin 的表达，并促进成骨分化。总之，CS NPs 通过激活自噬促进 BMSCs 中的骨形成和成骨分化。它们通过激活 mTOR/ULK1、诱导自噬，随后触发 WNT/β-catenin 途径来促进成骨细胞的分化和矿化来实现这一效果。
