Macrophage-Derived miRNA-Containing Exosomes Induce Peritendinous Fibrosis after Tendon Injury through the miR-21-5p/Smad7 Pathway

被引：95

作者：

Cui, Haomin ^{[1
,2
]}

He, Yu ^{[3
,4
]}

Chen, Shuai ^{[1
]}

Zhang, Deming ^{[5
]}

Yu, Yaling ^{[1
]}

Fan, Cunyi ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Orthopaed, 600 Yishan Rd, Shanghai 200233, Peoples R China

[2] Shanghai Univ Med & Hlth Sci, Shanghai Peoples Hosp East 6, Dept Orthopaed, Shanghai 201306, Peoples R China

[3] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Orthopaed, Beijing 100010, Peoples R China

[4] Peking Union Med Coll, Beijing 100010, Peoples R China

[5] Zhejiang Univ, Coll Mech Engn, Zhejiang Provinces Key Lab 3D Printing & Equipmen, Hangzhou 310058, Zhejiang, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2019年 / 14卷

基金：

中国国家自然科学基金;

关键词：

CELL-PROLIFERATION; ACHILLES-TENDON; INFLAMMATION; MIR-21; DIFFERENTIATION; TENDINOPATHY; FIBROBLASTS; BIOGENESIS; ACTIVATION; MECHANISMS;

D O I：

10.1016/j.omtn.2018.11.006

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Following tendon injury, the development of fibrotic healing response impairs tendon function and restricts tendon motion. Peritendinous tissue fibrosis poses a major clinical problem in hand surgery. Communication between macrophages and tendon cells has a critical role in regulating the tendon-healing process. Yet, the mechanisms employed by macrophages to control peritendinous fibrosis are not fully understood. Here we analyze the role of macrophages in tendon adhesion in mice by pharmacologically depleting them. Such macrophage-depleted mice have less peritendinous fibrosis formation around the injured tendon compared with wild-type littermates. Macrophage-depleted mice restart fibrotic tendon healing by treatment with bone marrow macrophage-derived exosomes. We show that bone marrow macrophages secrete exosomal miR-21-5p that directly targets Smad7, leading to the activation of fibrogenesis in tendon cells. These results demonstrate that intercellular crosstalk between bone marrow macrophages and tendon cells is mediated by macrophage-derived miR-21-5p-containing exosomes that control the fibrotic healing response, providing potential targets for the prevention and treatment of tendon adhesion.

引用

页码：114 / 130

页数：17