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Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets.
Zheng, Hao; Liu, Yuexuan; Deng, Yasi; Li, Yunzhe; Liu, Shiqi; Yang, Yong; Qiu, Yun; Li, Bin; Sheng, Wenbing; Liu, Jinzhi; Peng, Caiyun; Wang, Wei; Yu, Huanghe.
Afiliación
  • Zheng H; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Liu Y; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Deng Y; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Li Y; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Liu S; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Yang Y; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Qiu Y; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Li B; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Sheng W; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Liu J; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Peng C; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China.
  • Wang W; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China. wangwei402@hotmail.com.
  • Yu H; TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, 410208, China. yhh@hnucm.edu.cn.
Mol Med ; 30(1): 20, 2024 Feb 03.
Article en En | MEDLINE | ID: mdl-38310228
ABSTRACT
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Artritis Reumatoide / Factores de Transcripción NFATC Límite: Humans Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Artritis Reumatoide / Factores de Transcripción NFATC Límite: Humans Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China