Bioenergetic-active exosomes for cartilage regeneration and homeostasis maintenance

被引：14

作者：

Liu, Xulong ^{[1
,2
]}

Jiang, Shangtong ^{[1
,2
]}

Jiang, Ting ^{[1
,2
]}

Lan, Ziyang ^{[1
,2
]}

Zhang, Xin ^{[1
,2
]}

Zhong, Zhenyu ^{[1
,2
]}

Wu, Xiaodan ^{[1
,2
]}

Xu, Cunjing ^{[1
,2
]}

Du, Yingying ^{[1
,2
,3
,4
]}

Zhang, Shengmin ^{[1
,2
,3
,4
]}

机构：

[1] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Peoples R China

[2] Huazhong Univ Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan 430074, Peoples R China

[3] Natl Med Prod Adm, Res Base Regulatory Sci Med Devices, Wuhan 430074, Peoples R China

[4] Huazhong Univ Sci & Technol, Inst Regulatory Sci Med Devices, Wuhan 430074, Peoples R China

来源：

SCIENCE ADVANCES | 2024年 / 10卷 / 42期

基金：

中国国家自然科学基金;

关键词：

SUCCINATE-DEHYDROGENASE; MITOCHONDRIA; RECEPTOR; OSTEOARTHRITIS; ACTIVATION;

D O I：

10.1126/sciadv.adp7872

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Cartilage regeneration relies on adequate and continuous bioenergy supply to facilitate cellular differentiation and extracellular matrix synthesis. Chondrocytes frequently undergo energy stress under pathological conditions, characterized by disrupted cellular metabolism and reduced adenosine triphosphate (ATP) levels. However, there has limited progress in modulating energy metabolism for cartilage regeneration thus far. Here, we developed bioenergetic-active exosomes (Suc-EXO) to promote cartilage regeneration and homeostasis maintenance. Suc-EXO exhibited a 5.42-fold increase in ATP content, enabling the manipulation of cellular energy metabolism by fueling the TCA cycle. With continuous energy supply, Suc-EXO promoted BMSC chondrogenic differentiation via the P2X7-mediated PI3K-AKT pathway. Moreover, Suc-EXO improved chondrocyte anabolism and mitochondrial homeostasis via the P2X7-mediated SIRT3 pathway. In a rabbit cartilage defect model, the Suc-EXO-encapsulated hydrogel notably promoted cartilage regeneration and maintained neocartilage homeostasis, leading to 2.26 and 1.53 times increase in Col2 and ACAN abundance, respectively. These findings make a remarkable breakthrough in modulating energy metabolism for cartilage regeneration, offering immense potential for clinical translation.

引用

页数：18

共 56 条

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