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A novel nano-sized bioactive glass stimulates osteogenesis via the MAPK pathway

机译：一种新型的生物活性玻璃通过MAPK途径刺激成骨

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The aims of this study were to compare the osteogenic effects of a novel nano-sized bioactive glass (BG) and a traditional micron-sized BG, and to verify whether mitogen-activated protein kinases (MAPKs) are involved and play a part in BG’s osteoblast gene activation. It was found that the effect of a nano-sized BG on MAPK phosphorylation is better than the traditional 45S5 BG. We prepared extractions of the novel nano-sized 58S BG and traditional 45S5 BG and compared their effect on osteoblast-like cells’ (MG-63 cell) proliferation, osteogenic gene and protein expressions, matrix mineralization and MAPK activation. We further investigated the signal transducing effect of the MAPK pathway on the BG’s osteogenic gene activation. Our results showed that nano-58S extraction enhanced the MG-63 cells’ proliferation and osteogenic gene expressions of alkaline phosphatase (ALP), collagen type I (Col I), Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). The results of ELISA showed more Col I and OCN protein production in the BG groups than in the control group. Greater mineralized nodule formation was found in the nano-58S BG group using alizarin red S staining. We also found that nano-58S and 45S5 BG activated MAPKs, specifically the ERK and p38 pathways, using western blotting. After blocking the ERK or p38 pathway, real-time PCR showed the osteogenic gene activation induced by the BG extractions was inhibited. Blocking the ERK pathway induced a more obvious inhibitory effect on the genes’ normal expression and activation. The significance of this study is that we found that the ERK and p38 MAPK pathways are involved and play an important part in BG’s osteogenic gene activation. The effect of the nano-sized BG on MAPK phosphorylation, osteogenic gene activation, and osteoblast differentiation and mineralization is better than the traditional 45S5 BG.
机译：这项研究的目的是比较新型纳米生物活性玻璃（BG）和传统微米级BG的成骨作用，并验证是否有丝分裂原激活的蛋白激酶（MAPK）参与并在BG的过程中发挥作用成骨细胞基因激活。已经发现，纳米级BG对MAPK磷酸化的作用优于传统的45S5 BG。我们准备了新型58S BG和传统45S5 BG的提取物，并比较了它们对成骨样细胞（MG-63细胞）增殖，成骨基因和蛋白质表达，基质矿化和MAPK活化的影响。我们进一步研究了MAPK途径对BG成骨基因激活的信号转导作用。我们的结果表明，纳米58S提取可增强MG-63细胞的增殖，并增强碱性磷酸酶（ALP），I型胶原（Col I），Runt相关转录因子2（Runx2）和骨钙素（OCN）的成骨基因表达。 ELISA结果显示，BG组的Col I和OCN蛋白产量高于对照组。使用茜素红S染色在纳米58S BG组中发现了更大的矿化结节形成。我们还发现，使用蛋白质印迹法，纳米58S和45S5 BG激活了MAPK，特别是ERK和p38途径。阻断ERK或p38途径后，实时PCR显示BG提取物诱导的成骨基因激活受到抑制。阻断ERK通路对基因的正常表达和激活具有更明显的抑制作用。这项研究的意义在于，我们发现ERK和p38 MAPK通路与BG的成骨基因激活有关，并且起着重要的作用。纳米级BG对MAPK磷酸化，成骨基因激活以及成骨细胞分化和矿化的影响优于传统的45S5 BG。

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