NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages
Abstract Objective Synovial inflammation, which precedes other pathological changes in osteoarthritis (OA), is primarily initiated by activation and M1 polarization of macrophages. While macrophages play a pivotal role in the inflammatory process of OA, the mechanisms underlying their activation and...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-023-03230-4 |
| _version_ | 1797355572630126592 |
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| author | Changchuan Li Zhuji Ouyang Yuhsi Huang Sipeng Lin Shixun Li Jing Xu Taihe Liu Jionglin Wu Peidong Guo Zhong Chen Haoyu Wu Yue Ding |
| author_facet | Changchuan Li Zhuji Ouyang Yuhsi Huang Sipeng Lin Shixun Li Jing Xu Taihe Liu Jionglin Wu Peidong Guo Zhong Chen Haoyu Wu Yue Ding |
| author_sort | Changchuan Li |
| collection | DOAJ |
| description | Abstract Objective Synovial inflammation, which precedes other pathological changes in osteoarthritis (OA), is primarily initiated by activation and M1 polarization of macrophages. While macrophages play a pivotal role in the inflammatory process of OA, the mechanisms underlying their activation and polarization remain incompletely elucidated. This study aims to investigate the role of NOD2 as a reciprocal modulator of HMGB1/TLR4 signaling in macrophage activation and polarization during OA pathogenesis. Design We examined NOD2 expression in the synovium and determined the impact of NOD2 on macrophage activation and polarization by knockdown and overexpression models in vitro. Paracrine effect of macrophages on fibroblast-like synoviocytes (FLS) and chondrocytes was evaluated under conditions of NOD2 overexpression. Additionally, the in vivo effect of NOD2 was assessed using collagenase VII induced OA model in mice. Results Expression of NOD2 was elevated in osteoarthritic synovium. In vitro experiments demonstrated that NOD2 serves as a negative regulator of HMGB1/TLR4 signaling pathway. Furthermore, NOD2 overexpression hampered the inflammatory paracrine effect of macrophages on FLS and chondrocytes. In vivo experiments revealed that NOD2 overexpression mitigated OA in mice. Conclusions Supported by convincing evidence on the inhibitory role of NOD2 in modulating the activation and M1 polarization of synovial macrophages, this study provided novel insights into the involvement of innate immunity in OA pathogenesis and highlighted NOD2 as a potential target for the prevention and treatment of OA. |
| first_indexed | 2024-03-08T14:14:05Z |
| format | Article |
| id | doaj.art-57f2ff25b0ca485e9451423c8cc033f4 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-08T14:14:05Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-57f2ff25b0ca485e9451423c8cc033f42024-01-14T12:31:26ZengBMCArthritis Research & Therapy1478-63622023-12-0125111510.1186/s13075-023-03230-4NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophagesChangchuan Li0Zhuji Ouyang1Yuhsi Huang2Sipeng Lin3Shixun Li4Jing Xu5Taihe Liu6Jionglin Wu7Peidong Guo8Zhong Chen9Haoyu Wu10Yue Ding11Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityAbstract Objective Synovial inflammation, which precedes other pathological changes in osteoarthritis (OA), is primarily initiated by activation and M1 polarization of macrophages. While macrophages play a pivotal role in the inflammatory process of OA, the mechanisms underlying their activation and polarization remain incompletely elucidated. This study aims to investigate the role of NOD2 as a reciprocal modulator of HMGB1/TLR4 signaling in macrophage activation and polarization during OA pathogenesis. Design We examined NOD2 expression in the synovium and determined the impact of NOD2 on macrophage activation and polarization by knockdown and overexpression models in vitro. Paracrine effect of macrophages on fibroblast-like synoviocytes (FLS) and chondrocytes was evaluated under conditions of NOD2 overexpression. Additionally, the in vivo effect of NOD2 was assessed using collagenase VII induced OA model in mice. Results Expression of NOD2 was elevated in osteoarthritic synovium. In vitro experiments demonstrated that NOD2 serves as a negative regulator of HMGB1/TLR4 signaling pathway. Furthermore, NOD2 overexpression hampered the inflammatory paracrine effect of macrophages on FLS and chondrocytes. In vivo experiments revealed that NOD2 overexpression mitigated OA in mice. Conclusions Supported by convincing evidence on the inhibitory role of NOD2 in modulating the activation and M1 polarization of synovial macrophages, this study provided novel insights into the involvement of innate immunity in OA pathogenesis and highlighted NOD2 as a potential target for the prevention and treatment of OA.https://doi.org/10.1186/s13075-023-03230-4SynoviumMacrophagePolarizationNOD2 |
| spellingShingle | Changchuan Li Zhuji Ouyang Yuhsi Huang Sipeng Lin Shixun Li Jing Xu Taihe Liu Jionglin Wu Peidong Guo Zhong Chen Haoyu Wu Yue Ding NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages Arthritis Research & Therapy Synovium Macrophage Polarization NOD2 |
| title | NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages |
| title_full | NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages |
| title_fullStr | NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages |
| title_full_unstemmed | NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages |
| title_short | NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages |
| title_sort | nod2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages |
| topic | Synovium Macrophage Polarization NOD2 |
| url | https://doi.org/10.1186/s13075-023-03230-4 |
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