RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6R
ABSTRACT This study examined YTHDF2's role in modulating IL‐6R signaling to regulate synovial fibroblast inflammation and bone damage in rheumatoid arthritis (RA). Synovial tissues of RA patients were collected. Human fibroblast‐like synoviocyte (FLS), MH7A cell line, was induced with TNF‐α and...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.70010 |
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| author | Yan Zhang Xu‐Qing Cao Xiao‐Li Ma Yin‐Yan Guo Tao Zhang Li‐Li Wu Ya‐Shan Yang Chun‐Fang Hao Wei‐Li Liu Jiang‐Tao Guo |
| author_facet | Yan Zhang Xu‐Qing Cao Xiao‐Li Ma Yin‐Yan Guo Tao Zhang Li‐Li Wu Ya‐Shan Yang Chun‐Fang Hao Wei‐Li Liu Jiang‐Tao Guo |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | ABSTRACT This study examined YTHDF2's role in modulating IL‐6R signaling to regulate synovial fibroblast inflammation and bone damage in rheumatoid arthritis (RA). Synovial tissues of RA patients were collected. Human fibroblast‐like synoviocyte (FLS), MH7A cell line, was induced with TNF‐α and transfected. Cell proliferation was assessed using MTT and EdU assays; apoptosis was measured with flow cytometry, and migration and invasion were evaluated through scratch and Transwell assays. Lentiviral vectors designed to overexpress YTHDF2 or IL‐6R were created to study their effects in mice with collagen‐induced arthritis (CIA). Pathological changes of ankle joints in mice were observed, and TNF‐α, IL‐1β, and IL‐6 contents were determined. MMP3 and MMP9 levels were detected by Western blot, while YTHDF2 and IL‐6R were detected by RT‐qPCR and Western blot. The binding relationship between YTHDF2 and IL‐6R was studied. YTHDF2 in synovial tissues of RA patients was down‐regulated. Elevating YTHDF2 inhibited TNF‐α‐induced MH7A cell proliferation, migration, invasion, and pro‐inflammatory factors; Knocking down YTHDF2 showed the opposite effect. Upregulating YTHDF2 improved synovial inflammation and bone damage in CIA mice. IL‐6R in synovial tissues of patients was significantly up‐regulated and negatively correlated with YTHDF2 expression. YTHDF2 reduced IL‐6R mRNA stability in a m6A‐dependent manner. Overexpressing IL‐6R impaired the anti‐proliferating and anti‐inflammatory effect of YTHDF2 on TNF‐α‐induced MH7A cells. In CIA mice, overexpression of IL‐6R reversed the benefits on synovial inflammation and bone injury mediated by up‐regulating YTHDF2. YTHDF2 inhibits inflammation and bone damage in RA synovial fibroblasts by reducing the mRNA stability of IL‐6R. |
| format | Article |
| id | doaj-art-e5121d07c16d4e268a45bf330d3a4096 |
| institution | Kabale University |
| issn | 1607-551X 2410-8650 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj-art-e5121d07c16d4e268a45bf330d3a40962025-08-21T04:28:12ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502025-08-01418n/an/a10.1002/kjm2.70010RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6RYan Zhang0Xu‐Qing Cao1Xiao‐Li Ma2Yin‐Yan Guo3Tao Zhang4Li‐Li Wu5Ya‐Shan Yang6Chun‐Fang Hao7Wei‐Li Liu8Jiang‐Tao Guo9Department of Rheumatology and Immunology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan City ChinaDepartment of Neurology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan ChinaDepartment of Rheumatology and Immunology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan City ChinaDepartment of Rheumatology and Immunology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan City ChinaDepartment of Neurology Baoan District Central Hospital Shenzhen City ChinaDepartment of Rheumatology and Immunology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan City ChinaDepartment of Rheumatology and Immunology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan City ChinaDepartment of Rheumatology and Immunology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan City ChinaDepartment of Rheumatology and Immunology The Second Affiliated Hospital of the Chinese University of Hong Kong, Shenzhen (Longgang District People's Hospital of Shenzhen) Shenzhen ChinaDepartment of Rheumatology and Immunology People's Hospital of Ningxia Hui Autonomous Region (The Third Affiliated Hospital of Ningxia Medical University) Yinchuan City ChinaABSTRACT This study examined YTHDF2's role in modulating IL‐6R signaling to regulate synovial fibroblast inflammation and bone damage in rheumatoid arthritis (RA). Synovial tissues of RA patients were collected. Human fibroblast‐like synoviocyte (FLS), MH7A cell line, was induced with TNF‐α and transfected. Cell proliferation was assessed using MTT and EdU assays; apoptosis was measured with flow cytometry, and migration and invasion were evaluated through scratch and Transwell assays. Lentiviral vectors designed to overexpress YTHDF2 or IL‐6R were created to study their effects in mice with collagen‐induced arthritis (CIA). Pathological changes of ankle joints in mice were observed, and TNF‐α, IL‐1β, and IL‐6 contents were determined. MMP3 and MMP9 levels were detected by Western blot, while YTHDF2 and IL‐6R were detected by RT‐qPCR and Western blot. The binding relationship between YTHDF2 and IL‐6R was studied. YTHDF2 in synovial tissues of RA patients was down‐regulated. Elevating YTHDF2 inhibited TNF‐α‐induced MH7A cell proliferation, migration, invasion, and pro‐inflammatory factors; Knocking down YTHDF2 showed the opposite effect. Upregulating YTHDF2 improved synovial inflammation and bone damage in CIA mice. IL‐6R in synovial tissues of patients was significantly up‐regulated and negatively correlated with YTHDF2 expression. YTHDF2 reduced IL‐6R mRNA stability in a m6A‐dependent manner. Overexpressing IL‐6R impaired the anti‐proliferating and anti‐inflammatory effect of YTHDF2 on TNF‐α‐induced MH7A cells. In CIA mice, overexpression of IL‐6R reversed the benefits on synovial inflammation and bone injury mediated by up‐regulating YTHDF2. YTHDF2 inhibits inflammation and bone damage in RA synovial fibroblasts by reducing the mRNA stability of IL‐6R.https://doi.org/10.1002/kjm2.70010fibroblast‐like synoviocytesIL‐6Rinflammationrheumatoid arthritisYTHDF2 |
| spellingShingle | Yan Zhang Xu‐Qing Cao Xiao‐Li Ma Yin‐Yan Guo Tao Zhang Li‐Li Wu Ya‐Shan Yang Chun‐Fang Hao Wei‐Li Liu Jiang‐Tao Guo RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6R Kaohsiung Journal of Medical Sciences fibroblast‐like synoviocytes IL‐6R inflammation rheumatoid arthritis YTHDF2 |
| title | RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6R |
| title_full | RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6R |
| title_fullStr | RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6R |
| title_full_unstemmed | RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6R |
| title_short | RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL‐6R |
| title_sort | rna binding protein ythdf2 inhibits synovial fibroblast inflammation and bone injury in rheumatoid arthritis by reducing the mrna stability of il 6r |
| topic | fibroblast‐like synoviocytes IL‐6R inflammation rheumatoid arthritis YTHDF2 |
| url | https://doi.org/10.1002/kjm2.70010 |
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