Niobium promotes fracture healing in rats by regulating the PI3K-Akt signalling pathway: An in vivo and in vitro study.
Niobium promotes fracture healing in rats by regulating the PI3K-Akt signalling pathway: An in vivo and in vitro study.
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铌通过调节 PI3K-Akt 信号通路促进大鼠骨折愈合：一项体内和体外研究
DOI：
10.1016/j.jot.2022.08.007
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发表时间：
2022-11
影响因子：
6.6
通讯作者：
Hao, Yongqiang
中科院分区：
文献类型：
--
作者：
Tan, Jia;Li, Jiaxin;Cao, Bojun;Wu, Junxiang;Luo, Dinghao;Ran, Zhaoyang;Deng, Liang;Li, Xiaoping;Jiang, Wenbo;Xie, Kai;Wang, Lei;Hao, Yongqiang
稳定固定在骨折治疗中至关重要。目前，临床实践迫切需要具有骨诱导性、力学相容性和抗腐蚀性的最佳骨折固定装置。铌（Nb）的力学性能与骨组织相似，具有优异的生物相容性和抗腐蚀性，因此它有可能成为骨折内固定治疗最合适的固定材料。然而，在临床植入物领域，铌的应用并未受到太多关注。其促进骨折愈合的作用和机制仍不清楚。因此，本研究旨在通过体内和体外试验系统评估铌的成骨性能，以阐明其有效性。
进行了系统的体内和体外实验以评估铌的成骨特性。在体外实验中，评估了铌的生物相容性和促骨活性。并通过茜素红、碱性磷酸酶（ALP）染色和聚合酶链反应（PCR）测试评估了铌的骨诱导活性。在体内实验中，使用大鼠股骨骨折模型评估了铌促进骨折愈合的有效性和生物安全性。通过对骨痂组织基因测序结果的分析，检测到PI3K - Akt通路表达上调，并通过组织化学染色和蛋白质印迹（WB）实验进行了验证。
本研究中的实验证明，铌在体外具有优异的细胞黏附和促增殖作用，且无细胞毒性。此外，铌组的碱性磷酸酶活性、茜素红染色和半定量分析表明其对增强MC3T3 - E1细胞的成骨分化具有深远影响。我们还发现，在大鼠股骨骨折动物模型中，与使用Ti6Al4V相比，使用铌植入物可加速骨折愈合，并且通过组织学评估在体内证实了铌的生物安全性。此外，我们发现铌的成骨作用是通过激活PIK/Akt3信号通路实现的。
如本研究所示，铌在临床植入物中具有优异的生物安全性，并通过激活PI3K - Akt信号通路加速骨折愈合，具有良好的临床转化前景，可替代钛合金作为新型功能性植入物的材料。
Stable fixation is crucial in fracture treatment. Currently, optimal fracture fixation devices with osteoinductivity, mechanical compatibility, and corrosion resistance are urgently needed for clinical practice. Niobium (Nb), whose mechanical properties are similar to those of bone tissue, has excellent biocompatibility and corrosion resistance, so it has the potential to be the most appropriate fixation material for internal fracture treatment. However, not much attention has been paid to the use of Nb in the area of clinical implants. Yet its role and mechanism of promoting fracture healing remain unclear. Hence, this study aims at elucidating on the effectiveness of Nb by systematically evaluating its osteogenic performance via in vivo and ex vivo tests. Systematic in vivo and in vitro experiments were conducted to evaluate the osteogenic properties of Nb. In vitro experiments, the biocompatibility and osteopromoting activity of Nb were assessed. And the osteoinductive activity of Nb was assessed by alizarin red, ALP staining and PCR test. In vivo experiments, the effectiveness and biosafety of Nb in promoting fracture healing were evaluated using a rat femoral fracture model. Through the analysis of gene sequencing results of bone scab tissues, the upregulation of PI3K-Akt pathway expression was detected and it was verified by histochemical staining and WB experiments. Experiments in this study had proved that Nb had excellent in-vitro cell adhesion and proliferation-promoting effects without cytotoxicity. In addition, ALP activity, alizarin red staining and semi-quantitative analysis in the Nb group had indicated its profound impact on enhancing osteogenic differentiation of MC3T3-E1 cells. We also found that the use of Nb implants can accelerate fracture healing compared to that with Ti6Al4V using an animal model of femur fracture in rats, and the biosafety of Nb was confirmed in vivo via histological evaluation. Furthermore, we found that the osteogenic effects of Nb were achieved through activation of the PIK/Akt3 signalling pathway. As is shown in the present research, Nb possessed excellent biosafety in clinical implants and accelerated fracture healing by activating the PI3K-Akt signalling pathway, which had good prospects for clinical translation, and it can replace titanium alloy as a material for new functional implants.
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外源刺猬拮抗剂延迟，但不能防止年轻小鼠骨折愈合。
影响因子：
4.1
作者：
Liu X;McKenzie JA;Maschhoff CW;Gardner MJ;Silva MJ
通讯作者：
Silva MJ
影响因子：
3.7
作者：
Dong, Jun;Xu, Xiqiang;Tan, Bingyi
通讯作者：
Tan, Bingyi
影响因子：
5.3
作者：
DeFrancesco, Christopher J.;Canseco, Jose A.;Kamath, Atul F.
通讯作者：
Kamath, Atul F.
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
5.2
作者：
Lee, Min Young;Lim, Hyun Woo;Han, Ho Jae
通讯作者：
Han, Ho Jae