Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.
Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.
复制标题
可编程DNA水凝胶为增强椎间盘退变治疗中基于自噬的疗法提供了合适的微环境。
DOI：
10.1186/s12951-023-02109-5
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发表时间：
2023-09-28
影响因子：
10.2
通讯作者：
Hongxing, Shen
中科院分区：
文献类型：
--
作者：
Qingxin, Song;Kai, Jiang;Dandan, Zheng;Linyu, Jin;Xiuyuan, Chen;Yubo, Feng;Kun, Wang;Yingchao, Han;Hao, Chen;Jie, Song;Zhi, Chen;Hongxing, Shen
椎间盘退变（IVDD）的发病机制归因于细胞外基质代谢失调和髓核细胞（NPC）凋亡加剧。因此，治疗IVDD的潜在治疗策略包括重建细胞外基质内的代谢平衡和抑制过度的髓细胞凋亡。microRNA miR-5590在退行性髓核（NP）组织中表现出明显的差异表达，并直接影响DDX5的表达调控。这反过来又调节哺乳动物雷帕霉素靶蛋白（mTOR）磷酸化，从而影响自噬和细胞凋亡。然而，确保miRNA顺利递送到特定的损伤部位是一个重大挑战。为了解决这个问题，开发了一种多功能DNA水凝胶，随后通过球形核酸（SNAs）装载miR-5590用于治疗IVDD。水凝胶具有多功能性，有可能通过在损伤部位注射给药，导致miR-5590的一致和延长释放。这导致NP内产生遗传微环境，触发npc自噬的发生，随后抑制细胞凋亡。因此，这一过程调节了细胞外基质内的代谢平衡，从而阻碍了IVDD在体外和体内的进展。mirna和生物材料的融合为临床治疗IVDD提供了一种有希望的治疗策略。在线版本包含补充材料，可在10.1186/s12951-023-02109-5获得。
The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings. The online version contains supplementary material available at 10.1186/s12951-023-02109-5.
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影响因子：
5.1
作者：
Cai, Zhongxu;Li, Kunpeng;Xu, Hui
通讯作者：
Xu, Hui
影响因子：
4.9
作者：
Sudo T;Akeda K;Kawaguchi K;Hasegawa T;Yamada J;Inoue N;Masuda K;Sudo A
通讯作者：
Sudo A
间充质干细胞通过外泌体传递外源性miR-21抑制髓核细胞凋亡并减少椎间盘退变
影响因子：
5.3
作者：
Cheng X;Zhang G;Zhang L;Hu Y;Zhang K;Sun X;Zhao C;Li H;Li YM;Zhao J
通讯作者：
Zhao J
影响因子：
16.6
作者：
Legrand, Julien M. D.;Chan, Ai-Leen;Hobbs, Robin M.
通讯作者：
Hobbs, Robin M.
影响因子：
3
作者：
Masuda, K;Aota, Y;An, HS
通讯作者：
An, HS