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Interleukin-23 Mediates Osteoclastogenesis in Collagen-Induced Arthritis by Modulating MicroRNA-223.
Chen, Shih-Yao; Tsai, Ting-Chien; Li, Yuan-Tsung; Ding, Yun-Chiao; Wang, Chung-Teng; Hsieh, Jeng-Long; Wu, Chao-Liang; Wu, Po-Ting; Shiau, Ai-Li.
Afiliación
  • Chen SY; Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan.
  • Tsai TC; Department of Orthopaedics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan.
  • Li YT; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Ding YC; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Wang CT; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Hsieh JL; Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan.
  • Wu CL; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Wu PT; Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan.
  • Shiau AL; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Int J Mol Sci ; 23(17)2022 Aug 26.
Article en En | MEDLINE | ID: mdl-36077117
Interleukin-23 (IL-23) plays a pivotal role in rheumatoid arthritis (RA). IL-23 and microRNA-223 (miR-223) are both up-regulated and mediate osteoclastogenesis in mice with collagen-induced arthritis (CIA). The aim of this study was to examine the association between IL-23 and miR-223 in contributing to osteoclastogenesis and arthritis. Levels of IL-23p19 in joints of mice with CIA were determined. Lentiviral vectors expressing short hairpin RNA (shRNA) targeting IL-23p19 and lisofylline (LSF) were injected intraperitoneally into arthritic mice. Bone marrow-derived macrophages (BMMs) were treated with signal transducers and activators of transcription 4 (STAT4) specific shRNA and miR-223 sponge carried by lentiviral vectors in response to IL-23 stimulation. Treatment responses were determined by evaluating arthritis scores and histopathology in vivo, and detecting osteoclast differentiation and miR-223 levels in vitro. The binding of STAT4 to the promoter region of primary miR-223 (pri-miR-223) was determined in the Raw264.7 cell line. IL-23p19 expression was increased in the synovium of mice with CIA. Silencing IL-23p19 and inhibiting STAT4 activity ameliorates arthritis by reducing miR-223 expression. BMMs from mice in which STAT4 and miR-223 were silenced showed decreased osteoclast differentiation in response to IL-23 stimulation. IL-23 treatment increased the expression of miR-223 and enhanced the binding of STAT4 to the promoter of pri-miR-223. This study is the first to demonstrate that IL-23 promotes osteoclastogenesis by transcriptional regulation of miR-223 in murine macrophages and mice with CIA. Furthermore, our data indicate that LSF, a selective inhibitor of STAT4, should be an ideal therapeutic agent for treating RA through down-regulating miR-223-associated osteoclastogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / MicroARNs / Subunidad p19 de la Interleucina-23 Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / MicroARNs / Subunidad p19 de la Interleucina-23 Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza