2. Academic Validation
  3. GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases

GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases

  • Elife. 2023 Nov 6:12:e92142. doi: 10.7554/eLife.92142.
Gaoran Ge # 1,  Qianping Guo # 1 2,  Ying Zhou # 3,  Wenming Li 1,  Wei Zhang 1,  Jiaxiang Bai 4,  Qing Wang 1,  Huaqiang Tao 1,  Wei Wang 1,  Zhen Wang 5,  Minfeng Gan 1,  Yaozeng Xu 1,  Huilin Yang 1,  Bin Li 1 2 6,  Dechun Geng 1
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, China.
  • 2 Medical 3D Printing Center, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, China.
  • 3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, China.
  • 5 Department of Orthopaedics, Suzhou Kowloon Hospital Shanghai Jiao Tong University School of Medicine, Suzhou, China.
  • 6 Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • # Contributed equally.
PMID: 37929702 DOI: 10.7554/eLife.92142
Abstract

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.

Keywords

DNMTs; GLI1; macrophage; medicine; mouse; osteoclast; rheumatoid arthritis.

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