GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases
Rheumatoid arthritis (RA) is characterized by joint synovitis and bone destruction, the etiology of which remains to be explored. Many types of cells are involved in the progression of RA joint inflammation, among which the overactivation of M1 macrophages and osteoclasts has been thought to be an e...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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eLife Sciences Publications Ltd
2023-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/92142 |
| _version_ | 1797236884499333120 |
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| author | Gaoran Ge Qianping Guo Ying Zhou Wenming Li Wei Zhang Jiaxiang Bai Qing Wang Huaqiang Tao Wei Wang Zhen Wang Minfeng Gan Yaozeng Xu Huilin Yang Bin Li Dechun Geng |
| author_facet | Gaoran Ge Qianping Guo Ying Zhou Wenming Li Wei Zhang Jiaxiang Bai Qing Wang Huaqiang Tao Wei Wang Zhen Wang Minfeng Gan Yaozeng Xu Huilin Yang Bin Li Dechun Geng |
| author_sort | Gaoran Ge |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is characterized by joint synovitis and bone destruction, the etiology of which remains to be explored. Many types of cells are involved in the progression of RA joint inflammation, among which the overactivation of M1 macrophages and osteoclasts has been thought to be an essential cause of joint inflammation and bone destruction. Glioma-associated oncogene homolog 1 (GLI1) has been revealed to be closely linked to bone metabolism. In this study, GLI1 expression in the synovial tissue of RA patients was positively correlated with RA-related scores and was highly expressed in collagen-induced arthritis (CIA) mouse articular macrophage-like cells. The decreased expression and inhibition of nuclear transfer of GLI1 downregulated macrophage M1 polarization and osteoclast activation, the effect of which was achieved by modulation of DNA methyltransferases (DNMTs) via transcriptional regulation and protein interactions. By pharmacological inhibition of GLI1, the proportion of proinflammatory macrophages and the number of osteoclasts were significantly reduced, and the joint inflammatory response and bone destruction in CIA mice were alleviated. This study clarified the mechanism of GLI1 in macrophage phenotypic changes and activation of osteoclasts, suggesting potential applications of GLI1 inhibitors in the clinical treatment of RA. |
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| id | doaj.art-c2f175f23b9c463b810ad4c8f48e1563 |
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| language | English |
| last_indexed | 2024-04-24T17:10:57Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-c2f175f23b9c463b810ad4c8f48e15632024-03-28T12:39:56ZengeLife Sciences Publications LtdeLife2050-084X2023-11-011210.7554/eLife.92142GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferasesGaoran Ge0https://orcid.org/0000-0002-5535-7483Qianping Guo1Ying Zhou2Wenming Li3Wei Zhang4Jiaxiang Bai5https://orcid.org/0000-0002-3485-5563Qing Wang6Huaqiang Tao7Wei Wang8Zhen Wang9Minfeng Gan10Yaozeng Xu11Huilin Yang12Bin Li13Dechun Geng14https://orcid.org/0000-0003-4375-2803Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, China; Medical 3D Printing Center, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopaedics, Suzhou Kowloon Hospital Shanghai Jiao Tong University School of Medicine, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, China; Medical 3D Printing Center, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, ChinaRheumatoid arthritis (RA) is characterized by joint synovitis and bone destruction, the etiology of which remains to be explored. Many types of cells are involved in the progression of RA joint inflammation, among which the overactivation of M1 macrophages and osteoclasts has been thought to be an essential cause of joint inflammation and bone destruction. Glioma-associated oncogene homolog 1 (GLI1) has been revealed to be closely linked to bone metabolism. In this study, GLI1 expression in the synovial tissue of RA patients was positively correlated with RA-related scores and was highly expressed in collagen-induced arthritis (CIA) mouse articular macrophage-like cells. The decreased expression and inhibition of nuclear transfer of GLI1 downregulated macrophage M1 polarization and osteoclast activation, the effect of which was achieved by modulation of DNA methyltransferases (DNMTs) via transcriptional regulation and protein interactions. By pharmacological inhibition of GLI1, the proportion of proinflammatory macrophages and the number of osteoclasts were significantly reduced, and the joint inflammatory response and bone destruction in CIA mice were alleviated. This study clarified the mechanism of GLI1 in macrophage phenotypic changes and activation of osteoclasts, suggesting potential applications of GLI1 inhibitors in the clinical treatment of RA.https://elifesciences.org/articles/92142rheumatoid arthritismacrophageosteoclastGLI1DNMTs |
| spellingShingle | Gaoran Ge Qianping Guo Ying Zhou Wenming Li Wei Zhang Jiaxiang Bai Qing Wang Huaqiang Tao Wei Wang Zhen Wang Minfeng Gan Yaozeng Xu Huilin Yang Bin Li Dechun Geng GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases eLife rheumatoid arthritis macrophage osteoclast GLI1 DNMTs |
| title | GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases |
| title_full | GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases |
| title_fullStr | GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases |
| title_full_unstemmed | GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases |
| title_short | GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases |
| title_sort | gli1 facilitates collagen induced arthritis in mice by collaborative regulation of dna methyltransferases |
| topic | rheumatoid arthritis macrophage osteoclast GLI1 DNMTs |
| url | https://elifesciences.org/articles/92142 |
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