The exosome-like vesicles from osteoarthritic chondrocyte enhanced mature IL-1β production of macrophages and aggravated synovitis in osteoarthritis

被引：197

作者：

Ni, Zhenhong ^{[1
]}

Kuang, Liang ^{[1
]}

Chen, Hangang ^{[1
]}

Xie, Yangli ^{[1
]}

Zhang, Bin ^{[1
]}

Ouyang, Junjie ^{[1
]}

Wu, Jiangyi ^{[2
]}

Zhou, Siru ^{[1
]}

Chen, Liang ^{[3
]}

Su, Nan ^{[1
]}

Tan, QiaoYan ^{[1
]}

Luo, Xiaoqing ^{[1
]}

Chen, Bo ^{[3
]}

Chen, Shuai ^{[3
]}

Yin, Liangjun ^{[4
]}

Huang, Haiyang ^{[5
]}

Du, Xiaolan ^{[1
]}

Chen, Lin ^{[1
]}

机构：

[1] Third Mil Med Univ, Army Med Univ,State Key Lab Trauma Burns & Combin, Lab Rehabil Traumat Injuries,Lab Trauma,Ctr Bone, Daping Hosp,Res Inst Surg,Lab Prevent & Rehabil M, Chongqing 400042, Peoples R China

[2] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Ctr Joint Surg, Chongqing 400038, Peoples R China

[3] Third Mil Med Univ, Army Med Univ, Daping Hosp, Dept Spine Surg,Inst Surg Res, Chongqing 400042, Peoples R China

[4] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped Surg, Chongqing 400010, Peoples R China

[5] Qianjiang Nationality Hosp, Dept Orthoped Surg, Chongqing 409000, Peoples R China

来源：

CELL DEATH & DISEASE | 2019年 / 10卷 / 7期

基金：

中国国家自然科学基金;

关键词：

ARTICULAR-CARTILAGE VESICLES; KNEE OSTEOARTHRITIS; ACTIVATED MACROPHAGES; OSTEOPHYTE FORMATION; INFLAMMATION; PAIN; PROGRESSION; AUTOPHAGY; REGENERATION; DEGRADATION;

D O I：

10.1038/s41419-019-1739-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Synovitis, a common clinical symptom for osteoarthritis (OA) patients, is highly related to OA pathological progression and pain manifestation. The activated synovial macrophages have been demonstrated to play an important role in synovitis, but the mechanisms about macrophage activation are still not clear. In this study, we found that the exosome-like vesicles from osteoarthritic chondrocytes could be a new biological factor to stimulate inflammasome activation and increase mature IL-1 beta production in macrophages. The degraded cartilage explants produced more exosome-like vesicles than the nondegraded ones, while the exosome-like vesicles from chondrocytes could enter into joint synovium tissue and macrophages. Moreover, the exosome-like vesicles from osteoarthritic chondrocytes enhanced the production of mature IL-1 beta in macrophages. These vesicles could inhibit ATG4B expression via miR449a-5p, leading to inhibition of autophagy in LPS-primed macrophages. The decreased autophagy promoted the production of mitoROS, which further enhanced the inflammasome activation and subsequent IL-1 beta processing. Ultimately, the increase of mature IL-1 beta may aggravate synovial inflammation and promote the progression of OA disease. Our study provides a new perspective to understand the activation of synovial macrophages and synovitis in OA patients, which may be beneficial for therapeutic intervention in synovitis-related OA patients.

引用

页数：16

共 65 条

[1]

Association between clinical and sonographic synovitis in patients with painful knee osteoarthritis [J].