Nanorepairers Rescue Inflammation-Induced Mitochondrial Dysfunction in Mesenchymal Stem Cells.
Nanorepairers Rescue Inflammation-Induced Mitochondrial Dysfunction in Mesenchymal Stem Cells.
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纳米修复剂可挽救间充质干细胞中炎症引起的线粒体功能障碍
DOI：
10.1002/advs.202103839
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Zhai Q;Chen X;Fei D;Guo X;He X;Zhao W;Shi S;Gooding JJ;Jin F;Jin Y;Li B
组织特异性间充质干细胞（MSC）中的线粒体功能障碍在细胞命运和慢性炎症相关性骨疾病（如牙周炎和骨关节炎）的发病率中起着关键作用。然而，仍然没有有效的方法通过生理恢复线粒体和MSC的功能来治疗慢性炎症相关的骨疾病。在此，首次发现慢性炎症导致过量的Ca 2+从内质网转移到线粒体，这导致线粒体钙超载并进一步损伤线粒体。此外，由于在慢性炎症条件下通过激活Wnt/β-连环蛋白途径抑制线粒体自噬，受损的线粒体在MSC中持续积累，损害MSC的分化。基于该机制发现，制造细胞内微环境（酯酶和低pH）响应性纳米颗粒以捕获MSC中线粒体周围的Ca 2+，从而调节MSC线粒体钙通量以对抗线粒体功能障碍。此外，相同的纳米颗粒能够将siRNA递送至MSC以抑制Wnt/β-连环蛋白途径并调节最初功能失调的线粒体的线粒体自噬。这些精密设计的纳米颗粒被称为“纳米修复剂”，在生理上恢复线粒体和MSC的功能，从而有效治疗牙周炎和骨关节炎。这一概念可以通过线粒体质量控制干预扩展到其他疾病的治疗。慢性炎症导致线粒体Ca ~（2+）超载，线粒体自噬功能受到抑制，导致骨髓间充质干细胞（mesenchymal stem cells，MSCs）分化障碍。基于力学研究结果，精密工程纳米颗粒通过捕获线粒体周围的Ca 2+并抑制Wnt/β-catenin通路，生理性地恢复线粒体和MSC的功能，为牙周炎和骨关节炎提供有效的治疗。
Mitochondrial dysfunction in tissue‐specific mesenchymal stem cells (MSCs) plays a critical role in cell fate and the morbidity of chronic inflammation‐associated bone diseases, such as periodontitis and osteoarthritis. However, there is still no effective method to cure chronic inflammation‐associated bone diseases by physiologically restoring the function of mitochondria and MSCs. Herein, it is first found that chronic inflammation leads to excess Ca2+ transfer from the endoplasmic reticulum to mitochondria, which causes mitochondrial calcium overload and further damage to mitochondria. Furthermore, damaged mitochondria continuously accumulate in MSCs due to the inhibition of mitophagy by activating the Wnt/β‐catenin pathway under chronic inflammatory conditions, impairing the differentiation of MSCs. Based on the mechanistic discovery, intracellular microenvironment (esterase and low pH)‐responsive nanoparticles are fabricated to capture Ca2+ around mitochondria in MSCs to regulate MSC mitochondrial calcium flux against mitochondrial dysfunction. Furthermore, the same nanoparticles are able to deliver siRNA to MSCs to inhibit the Wnt/β‐catenin pathway and regulate mitophagy of the originally dysfunctional mitochondria. These precision‐engineered nanoparticles, referred to as “nanorepairers,” physiologically restore the function of mitochondria and MSCs, resulting in effective therapy for periodontitis and osteoarthritis. The concept can potentially be expanded to the treatment of other diseases via mitochondrial quality control intervention. Chronic inflammation leads to mitochondrial Ca2+ overload and the inhibition of mitophagy, resulting in the impaired differention of mesenchymal stem cells (MSCs). Based on mechanistical findings, precision‐engineered nanoparticles physiologically restore the function of mitochondria and MSCs by capturing Ca2+ around mitochondria and inhibiting Wnt/β‐catenin pathway, providing effective therapy for periodontitis and osteoarthritis.
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DOI：
10.1083/jcb.201708191
发表时间：
2018-04-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bernkopf DB;Jalal K;Brückner M;Knaup KX;Gentzel M;Schambony A;Behrens J
通讯作者：
Behrens J
影响因子：
82.9
作者：
通讯作者：
--
肝素改善骨髓间充质干细胞治疗：肝素抗凝治疗提高骨髓间充质干细胞治疗的安全性和治疗效果
影响因子：
12.4
作者：
Liao L;Shi B;Chang H;Su X;Zhang L;Bi C;Shuai Y;Du X;Deng Z;Jin Y
通讯作者：
Jin Y
影响因子：
7.5
作者：
Li C;Li B;Dong Z;Gao L;He X;Liao L;Hu C;Wang Q;Jin Y
通讯作者：
Jin Y
影响因子：
16.6
作者：
Huang, Jian;Zhao, Lan;Chen, Di
通讯作者：
Chen, Di