Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading
Summary: Evidence indicates that mechanical loading plays an important role in osteoarthritis (OA) progression, while the specific pathological changes of the synovium under excessive mechanical loading are unclear. Results showed that excessive mechanical loading caused pro-inflammation of synovial...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225003918 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849729876526891008 |
|---|---|
| author | Wen Tang Jian-bin Yin Ren-gui Lin Chun-yu Wu Jia-luo Huang Jin-jian Zhu Ling-feng Yang Guang-ming Li Dao-zhang Cai Liang-liang Liu Yan-li Liu Hai-yan Zhang |
| author_facet | Wen Tang Jian-bin Yin Ren-gui Lin Chun-yu Wu Jia-luo Huang Jin-jian Zhu Ling-feng Yang Guang-ming Li Dao-zhang Cai Liang-liang Liu Yan-li Liu Hai-yan Zhang |
| author_sort | Wen Tang |
| collection | DOAJ |
| description | Summary: Evidence indicates that mechanical loading plays an important role in osteoarthritis (OA) progression, while the specific pathological changes of the synovium under excessive mechanical loading are unclear. Results showed that excessive mechanical loading caused pro-inflammation of synovial macrophages, which has been confirmed to exist in OA. High Rapgef3 expression level was found in RNA sequencing of RAW246.7 subjected to 0.5 Hz and 20% cyclic tensile strain. We verified this in the synovium of patients with OA and destabilization of the medial meniscus (DMM)-OA mice. Interestingly, the Rapgef3 content of chondrocytes was very low. Primary chondrocytes treated with Rapgef3 alone did not show metabolic phenotype, but an OA phenotype appeared when treated with Rapgef3-stimulated macrophage culture supernatant. Mechanically, excessive mechanical loading activated p65-nuclear factor κB (NF-κB) pathway through Rapgef3, which promoted the inflammation of macrophage, resulting in severe articular cartilage injury. Intra-articular Rapgef3 knockout reversed synovitis and cartilage degeneration, which might provide a therapeutic target for OA. |
| format | Article |
| id | doaj-art-861e22a671334dd29b24ed7cb6d7b522 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-861e22a671334dd29b24ed7cb6d7b5222025-08-20T03:09:03ZengElsevieriScience2589-00422025-05-0128511213110.1016/j.isci.2025.112131Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loadingWen Tang0Jian-bin Yin1Ren-gui Lin2Chun-yu Wu3Jia-luo Huang4Jin-jian Zhu5Ling-feng Yang6Guang-ming Li7Dao-zhang Cai8Liang-liang Liu9Yan-li Liu10Hai-yan Zhang11Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China; Corresponding authorThe Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China; Corresponding authorDepartment of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China; Corresponding authorSummary: Evidence indicates that mechanical loading plays an important role in osteoarthritis (OA) progression, while the specific pathological changes of the synovium under excessive mechanical loading are unclear. Results showed that excessive mechanical loading caused pro-inflammation of synovial macrophages, which has been confirmed to exist in OA. High Rapgef3 expression level was found in RNA sequencing of RAW246.7 subjected to 0.5 Hz and 20% cyclic tensile strain. We verified this in the synovium of patients with OA and destabilization of the medial meniscus (DMM)-OA mice. Interestingly, the Rapgef3 content of chondrocytes was very low. Primary chondrocytes treated with Rapgef3 alone did not show metabolic phenotype, but an OA phenotype appeared when treated with Rapgef3-stimulated macrophage culture supernatant. Mechanically, excessive mechanical loading activated p65-nuclear factor κB (NF-κB) pathway through Rapgef3, which promoted the inflammation of macrophage, resulting in severe articular cartilage injury. Intra-articular Rapgef3 knockout reversed synovitis and cartilage degeneration, which might provide a therapeutic target for OA.http://www.sciencedirect.com/science/article/pii/S2589004225003918Biological sciencesMolecular biologyImmunologyBiomechanicsTranscriptomics |
| spellingShingle | Wen Tang Jian-bin Yin Ren-gui Lin Chun-yu Wu Jia-luo Huang Jin-jian Zhu Ling-feng Yang Guang-ming Li Dao-zhang Cai Liang-liang Liu Yan-li Liu Hai-yan Zhang Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading iScience Biological sciences Molecular biology Immunology Biomechanics Transcriptomics |
| title | Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading |
| title_full | Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading |
| title_fullStr | Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading |
| title_full_unstemmed | Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading |
| title_short | Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading |
| title_sort | rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading |
| topic | Biological sciences Molecular biology Immunology Biomechanics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225003918 |
| work_keys_str_mv | AT wentang rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT jianbinyin rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT renguilin rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT chunyuwu rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT jialuohuang rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT jinjianzhu rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT lingfengyang rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT guangmingli rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT daozhangcai rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT liangliangliu rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT yanliliu rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading AT haiyanzhang rapgef3modulatesmacrophagereprogrammingandexacerbatessynovitisandosteoarthritisunderexcessivemechanicalloading |