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Interleukin-13 reduces bone erosion in rheumatoid arthritis by up-regulating osteoprotegerin expression in fibroblast-like synoviocytes : an in vitro and in vivo study
Z. Chen1, Z. Cheng2, Z. Tang3, M. Li4, X. Tang5, H. Zhang6, L. Sun7
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. xjtang09@163.com
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. huayong.zhang@nju.edu.cn
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
CER16340
2023 Vol.41, N°11
PI 2151, PF 2161
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PMID: 36995338 [PubMed]
Received: 05/11/2022
Accepted : 27/02/2023
In Press: 27/03/2023
Published: 14/11/2023
Abstract
OBJECTIVES:
Bone erosion in rheumatoid arthritis (RA) is partly caused by excessive activation of osteoclasts. Osteoclasts can be derived from RA synovium and their differentiation can be inhibited by osteoprotegerin (OPG), a decoy receptor of the osteoclastogenesis-promoting cytokine receptor activator of nuclear factor κB ligand (RANKL). Fibroblast-like synoviocytes (FLSs) are the main stromal cells in the synovium that can secret OPG. The OPG secretion of FLSs can be modulated by various cytokines. Interleukin (IL)-13 can alleviate bone erosion in RA mouse models, but the mechanisms remain unclear. Therefore, we aimed to investigate whether IL-13 can induce OPG secretion by RA-FLSs, thus ameliorating bone destruction in RA by inhibiting osteoclast differentiation.
METHODS:
OPG, RANKL, and IL-13 receptors expression by RA-FLSs were evaluated by RT-qPCR. OPG secretion was determined by ELISA. Western blot was performed to analyse OPG expression and the activation of the STAT6 pathway. IL-13 and (or) OPG siRNA pre-treated RA-FLSs conditioned medium were used in osteoclast induction to test if IL-13 can inhibit osteoclastogenesis by up-regulating OPG in RA-FLSs. Micro-CT and immunofluorescence were performed to determine if IL-13 can induce OPG expression and alleviate bone erosion in vivo.
RESULTS:
IL-13 can promote OPG expression of RA-FLSs, and the promotion can be overcome by IL-13Rα1 or IL-13Rα2 siRNA transfection, or STAT6 inhibitor. Osteoclast differentiation can be inhibited by IL-13 pre-treated RA-FLSs conditioned medium. The inhibition can be reversed by OPG siRNA transfection. IL-13 injection can increase OPG expression in the joints while reducing bone destruction in collagen-induced arthritis mice.
CONCLUSIONS:
IL-13 can inhibit osteoclastogenesis by up-regulating OPG in RA-FLSs through IL-13 receptors via the STAT6 pathway, thus may ameliorate bone erosion in RA.
