M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator

被引：80

作者：

Wang, Yili ^{[1
,2
,3
,4
,5
]}

Lin, Qiushui ^{[6
]}

Zhang, Hao ^{[1
,4
,5
]}

Wang, Sicheng ^{[1
,7
]}

Cui, Jin ^{[1
,4
,5
]}

Hu, Yan ^{[1
,5
]}

Liu, Jinlong ^{[1
,4
,5
,8
]}

Li, Mengmeng ^{[1
,4
,5
]}

Zhang, Kun ^{[9
]}

Zhou, Fengjin ^{[9
]}

Jing, Yingying ^{[1
,4
,5
,10
,11
]}

Geng, Zhen ^{[1
,4
,5
]}

Su, Jiacan ^{[1
,4
,5
,12
]}

机构：

[1] Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China

[2] Shanghai Univ, Sch Med, Shanghai 200444, Peoples R China

[3] Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China

[4] Shanghai Univ, Organoid Res Ctr, Shanghai 200444, Peoples R China

[5] Shanghai Univ, Natl Ctr Translat Med Shanghai SHU Branch, Shanghai 200444, Peoples R China

[6] Naval Med Univ, Affiliated Hosp 1, Dept Spine Surg, Shanghai 200433, Peoples R China

[7] Shanghai Zhongye Hosp, Dept Orthoped, Shanghai 200941, Peoples R China

[8] Second Mil Med Univ, Changhai Hosp, Dept Orthoped Trauma, Shanghai 200433, Peoples R China

[9] Xi An Jiao Tong Univ, Honghui Hosp, Dept Orthoped, Xian 710000, Peoples R China

[10] Shanghai Univ, Suzhou Innovat Ctr, Suzhou 215000, Jiangsu, Peoples R China

[11] Shanghai Univ, Shaoxing Inst Technol, Shaoxing 312000, Zhejiang, Peoples R China

[12] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Orthoped, Sch Med, Shanghai 200092, Peoples R China

来源：

BIOACTIVE MATERIALS | 2023年 / 28卷

基金：

中国国家自然科学基金;

关键词：

M2-exosomes; Diabetic fracture healing; Osteoimmune microenvironment; Macrophage polarization; PI3K; AKT signaling pathway; BONE LOSS; MICE;

D O I：

10.1016/j.bioactmat.2023.05.018

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing. Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes, which respectively exhibit pro-inflammatory or anti-inflammatory functions. Therefore, modulation of macro-phage polarization to the M2 subtype is beneficial for fracture healing. Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity. In this study, we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures. The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages, thereby accelerating diabetic fracture healing. We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway. Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.

引用

页码：273 / 283

页数：11

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