ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis
Abstract Objective Osteoarthritis (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 p...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-023-03238-w |
| _version_ | 1797355614451531776 |
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| author | Kai Chen Huaqiang Tao Pengfei Zhu Miao Chu Xueyan Li Yi Shi Liyuan Zhang Yaozeng Xu Shujun Lv Lixin Huang Wei Huang Dechun Geng |
| author_facet | Kai Chen Huaqiang Tao Pengfei Zhu Miao Chu Xueyan Li Yi Shi Liyuan Zhang Yaozeng Xu Shujun Lv Lixin Huang Wei Huang Dechun Geng |
| author_sort | Kai Chen |
| collection | DOAJ |
| description | Abstract Objective Osteoarthritis (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. Methods Both 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. Results Our sequencing analysis revealed significant upregulation of the MAPK signaling cascade and ADAM8 gene expression in IL-1β-induced FLSs. The in vitro results demonstrated that ADAM8 blockade inhibited the invasion and migration of IL-1β-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. Conclusions ADAM8 could be a promising therapeutic target for treating OA by targeting synovial inflammation. |
| first_indexed | 2024-03-08T14:14:39Z |
| format | Article |
| id | doaj.art-eeb5a94ecb65445f96e1218fdd153fc3 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-08T14:14:39Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-eeb5a94ecb65445f96e1218fdd153fc32024-01-14T12:31:30ZengBMCArthritis Research & Therapy1478-63622024-01-0126111710.1186/s13075-023-03238-wADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritisKai Chen0Huaqiang Tao1Pengfei Zhu2Miao Chu3Xueyan Li4Yi Shi5Liyuan Zhang6Yaozeng Xu7Shujun Lv8Lixin Huang9Wei Huang10Dechun Geng11Department of Orthopedics, The First Affiliated Hospital of Soochow UniversityDepartment of Orthopedics, The First Affiliated Hospital of Soochow UniversityDepartment of Orthopedics, The First Affiliated Hospital of Soochow UniversityDepartment of Orthopedics, The First Affiliated Hospital of Soochow UniversityAnesthesiology department, Suzhou Municipal Hospital (North District), Nanjing Medical University Affiliated Suzhou HospitalAnesthesiology department, Suzhou Municipal Hospital (North District), Nanjing Medical University Affiliated Suzhou HospitalAnesthesiology department, Suzhou Municipal Hospital (North District), Nanjing Medical University Affiliated Suzhou HospitalDepartment of Orthopedics, The First Affiliated Hospital of Soochow UniversityDepartment of Orthopedics, Hai’an People’s HospitalDepartment of Orthopedics, The First Affiliated Hospital of Soochow UniversityDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow UniversityAbstract Objective Osteoarthritis (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. Methods Both 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. Results Our sequencing analysis revealed significant upregulation of the MAPK signaling cascade and ADAM8 gene expression in IL-1β-induced FLSs. The in vitro results demonstrated that ADAM8 blockade inhibited the invasion and migration of IL-1β-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. Conclusions ADAM8 could be a promising therapeutic target for treating OA by targeting synovial inflammation.https://doi.org/10.1186/s13075-023-03238-wOsteoarthritisFibroblast-like synoviocytesADAM8InflammationMAPK |
| spellingShingle | Kai Chen Huaqiang Tao Pengfei Zhu Miao Chu Xueyan Li Yi Shi Liyuan Zhang Yaozeng Xu Shujun Lv Lixin Huang Wei Huang Dechun Geng ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis Arthritis Research & Therapy Osteoarthritis Fibroblast-like synoviocytes ADAM8 Inflammation MAPK |
| title | ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis |
| title_full | ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis |
| title_fullStr | ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis |
| title_full_unstemmed | ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis |
| title_short | ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis |
| title_sort | adam8 silencing suppresses the migration and invasion of fibroblast like synoviocytes via fscn1 mapk cascade in osteoarthritis |
| topic | Osteoarthritis Fibroblast-like synoviocytes ADAM8 Inflammation MAPK |
| url | https://doi.org/10.1186/s13075-023-03238-w |
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