ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis

被引:3
|
作者
Chen, Kai [1 ,3 ]
Tao, Huaqiang [1 ]
Zhu, Pengfei [1 ]
Chu, Miao [1 ,5 ]
Li, Xueyan [2 ]
Shi, Yi [2 ]
Zhang, Liyuan [2 ]
Xu, Yaozeng [1 ]
Lv, Shujun [3 ]
Huang, Lixin [1 ]
Huang, Wei [4 ]
Geng, Dechun [1 ]
机构
[1] Soochow Univ, Dept Orthoped, Affiliated Hosp 1, Shizi St 188, Suzhou, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Suzhou Hosp, Anesthesiol Dept, Suzhou Municipal Hosp North District, 242,Guangji Rd, Suzhou, Jiangsu, Peoples R China
[3] Haian Peoples Hosp, Dept Orthoped, Zhongba Rd 17, Haian, Jiangsu, Peoples R China
[4] Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Orthoped, Div Life Sci & Med, 17 Lujiang Rd, Hefei, Anhui, Peoples R China
[5] Yixing Peopless Hosp, Dept Orthoped, Xincheng Rd 1588, Yixing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Osteoarthritis; Fibroblast-like synoviocytes; ADAM8; Inflammation; MAPK; INFLAMMATION; KNEE; INTERLEUKIN-1-BETA; MACROPHAGES; METASTASIS; TARGET; MATRIX; GROWTH; ALPHA;
D O I
10.1186/s13075-023-03238-w
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
ObjectiveOsteoarthritis (OA) is a degenerative joint disease that affects elderly populations worldwide, causing pain and disability. Alteration of the fibroblast-like synoviocytes (FLSs) phenotype leads to an imbalance in the synovial inflammatory microenvironment, which accelerates the progression of OA. Despite this knowledge, the specific molecular mechanisms of the synovium that affect OA are still unclear.MethodsBoth in vitro and in vivo experiments were undertaken to explore the role of ADAM8 playing in the synovial inflammatory of OA. A small interfering RNA (siRNA) was targeting ADAM8 to intervene. High-throughput sequencing was also used.ResultsOur sequencing analysis revealed significant upregulation of the MAPK signaling cascade and ADAM8 gene expression in IL-1 beta-induced FLSs. The in vitro results demonstrated that ADAM8 blockade inhibited the invasion and migration of IL-1 beta-induced FLSs, while also suppressing the expression of related matrix metallomatrix proteinases (MMPs). Furthermore, our study revealed that inhibiting ADAM8 weakened the inflammatory protein secretion and MAPK signaling networks in FLSs. Mechanically, it revealed that inhibiting ADAM8 had a significant effect on the expression of migration-related signaling proteins, specifically FSCN1. When siADAM8 was combined with BDP-13176, a FSCN1 inhibitor, the migration and invasion of FLSs was further inhibited. These results suggest that FSCN1 is a crucial downstream factor of ADAM8 in regulating the biological phenotypes of FLSs. The in vivo experiments demonstrated that ADAM8 inhibition effectively reduced synoviocytes inflammation and alleviated the progression of OA in rats.ConclusionsADAM8 could be a promising therapeutic target for treating OA by targeting synovial inflammation.
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页数:17
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