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生物功能镁涂层Ti6Al4V支架通过激活AMPK/mTOR/ULK1信号通路促进骨肉瘤中自噬依赖性凋亡。

Biofunctional magnesium-coated Ti6Al4V scaffolds promote autophagy-dependent apoptosis in osteosarcoma by activating the AMPK/mTOR/ULK1 signaling pathway.

作者信息

Wei X, Tang Z, Wu H, Zuo X, Dong H, Tan L, Wang W, Liu Y, Wu Z, Shi L, Wang N, Li X, Xiao X, Guo Z

机构信息

Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.

Institute of Metal Research, Chinese Academy of Science, Shenyang, 110016, PR China.

出版信息

Mater Today Bio. 2021 Oct 12;12:100147. doi: 10.1016/j.mtbio.2021.100147. eCollection 2021 Sep.

Abstract

The recurrence of osteosarcoma (OS) after reconstruction using Ti6Al4V prostheses remains a major problem in the surgical treatment of OS. Modification of the surfaces of Ti6Al4V prostheses with antitumor functions is an important strategy for improving therapeutic outcomes. Magnesium (Mg) coating has been shown to be multifunctional: it exhibits osteogenic and angiogenic properties and the potential to inhibit OS. In this study, we determined the proper concentration of released Mg with respect to OS inhibition and biosafety and evaluated the anti-OS effects of Mg-coated Ti6Al4V scaffolds. We found that the release of Mg during short-term and long-term degradation could significantly inhibit the proliferation and migration of HOS and 143B cells. Increased cell apoptosis and excessive autophagy were also observed, and further evidence of AMPK/mTOR/ULK1 signaling pathway activation was obtained both and , which suggested that the biofunctional scaffolds induce OS inhibition. Our study demonstrates the ability of an Mg coating to inhibit OS and may contribute to the further application of Mg-coated Ti6Al4V prostheses.

摘要

使用Ti6Al4V假体进行重建后骨肉瘤(OS)的复发仍然是骨肉瘤外科治疗中的一个主要问题。对具有抗肿瘤功能的Ti6Al4V假体表面进行改性是改善治疗效果的重要策略。镁(Mg)涂层已被证明具有多种功能:它具有成骨和血管生成特性以及抑制骨肉瘤的潜力。在本研究中,我们确定了与骨肉瘤抑制和生物安全性相关的镁释放的合适浓度,并评估了镁涂层Ti6Al4V支架的抗骨肉瘤作用。我们发现,在短期和长期降解过程中镁的释放可显著抑制HOS和143B细胞的增殖和迁移。还观察到细胞凋亡增加和过度自噬,并且在体内和体外均获得了AMPK/mTOR/ULK1信号通路激活的进一步证据,这表明生物功能支架可诱导骨肉瘤抑制。我们的研究证明了镁涂层抑制骨肉瘤的能力,并可能有助于镁涂层Ti6Al4V假体的进一步应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1a/8523865/e78826f9b30b/ga1.jpg

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