Chondroprotective functions of neutrophil-derived extracellular vesicles by promoting the production of secreted frizzled-related protein 5 in cartilage

被引：1

作者：

Kitahara, Keita ^{[1
]}

Ebata, Taku ^{[1
]}

Liyile, Chen ^{[1
]}

Nishida, Yoshio ^{[1
]}

Ogawa, Yuki ^{[1
]}

Tokuhiro, Taiki ^{[1
]}

Shiota, Junki ^{[1
]}

Nagano, Tatsuya ^{[2
]}

Takasuka, Taichi E. ^{[2
]}

Endo, Tsutomu ^{[1
]}

Shimizu, Tomohiro ^{[1
]}

Alhasan, Hend ^{[1
]}

Asano, Tsuyoshi ^{[1
]}

Takahashi, Daisuke ^{[1
]}

Homan, Kentaro ^{[1
]}

Onodera, Tomohiro ^{[1
]}

Kadoya, Ken ^{[1
]}

Terkawi, M. Alaa ^{[1
]}

Iwasaki, Norimasa ^{[1
]}

机构：

[1] Hokkaido Univ, Fac Med, Grad Sch Med, Dept Orthoped Surg, Kita 15,Nish 7,Kita Ku, Sapporo 0608638, Japan

[2] Hokkaido Univ, Res Fac Agr, Kita 9,Nishi 9,Kitaku, Sapporo 0608589, Japan

来源：

CELL COMMUNICATION AND SIGNALING | 2024年 / 22卷 / 01期

基金：

日本学术振兴会;

关键词：

GROWTH-FACTOR-BETA; NF-KAPPA-B; INFLAMMATORY RESPONSE; ARTICULAR-CARTILAGE; OSTEOARTHRITIS; DESTRUCTION; ARTHRITIS; EXOSOMES;

D O I：

10.1186/s12964-024-01953-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

BackgroundOsteoarthritis (OA) is the most common degenerative joint disease characterized by cartilage degradation and various degrees of inflammation in the synovium. Growing evidence highlights that neutrophil extracellular vesicles (EVs) play a protective role in arthritic joints by promoting the resolution of inflammation and the synthesis of proteoglycans in cartilage. However, this homeostatic function is dependent on the activation state of neutrophils and the surrounding environment/tissues. Hence, we explored the chondroprotective functions of neutrophil-derived EVs under different stimulation conditions and the underlying molecular mechanism.MethodsHuman blood-derived neutrophils, murine bone marrow-derived neutrophils, C-28I2 cells and primary chondrocytes were used. Neutrophils were stimulated with different cytokines, and their EVs were isolated for chondrocyte stimulation and further subjected to RNA-sequencing analysis. Two experimental murine OA models were used, and the treatment was performed by intraarticular injections.ResultsConditioned medium from neutrophils stimulated with TGF-beta (N-beta) had the greatest inhibitory effect on the expression of catabolic factors in stimulated chondrocytes. These protective effects were not impaired when conditioned medium of N-beta from AnxA1-deficient mice was used. Consistent with these results, EVs isolated from N-beta significantly reduced the expression of catabolic factors in stimulated chondrocytes. Bulk RNA-seq analysis revealed that secreted frizzled-related protein 5 (SFRP5) is upregulated in N-beta-EV-stimulated chondrocytes. Furthermore, recombinant SFRP5 treatment significantly reduced the expression of catabolic factors in vitro and catabolic process in experimental murine OA models.ConclusionsThe current study emphasizes the potential therapeutic application of neutrophils in OA and provides new knowledge on the molecular mechanisms underlying their function.

引用

页数：12

共 2 条

[1] Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway
Minghui Sun
Weijun Wang
Lingtian Min
Cheng Chen
Qing Li
Wenjie Weng
Journal of Orthopaedic Surgery and Research, 16
[2] Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway
Sun, Minghui
Wang, Weijun
Min, Lingtian
Chen, Cheng
Li, Qing
Weng, Wenjie
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH, 2021, 16 (01)

← 1 →