Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets

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 o...

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Main Authors: Hao Zheng, Yuexuan Liu, Yasi Deng, Yunzhe Li, Shiqi Liu, Yong Yang, Yun Qiu, Bin Li, Wenbing Sheng, Jinzhi Liu, Caiyun Peng, Wei Wang, Huanghe Yu
Format: Article
Language:English
Published: BMC 2024-02-01
Series:Molecular Medicine
Subjects:
Online Access:https://doi.org/10.1186/s10020-024-00788-w
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author Hao Zheng
Yuexuan Liu
Yasi Deng
Yunzhe Li
Shiqi Liu
Yong Yang
Yun Qiu
Bin Li
Wenbing Sheng
Jinzhi Liu
Caiyun Peng
Wei Wang
Huanghe Yu
author_facet Hao Zheng
Yuexuan Liu
Yasi Deng
Yunzhe Li
Shiqi Liu
Yong Yang
Yun Qiu
Bin Li
Wenbing Sheng
Jinzhi Liu
Caiyun Peng
Wei Wang
Huanghe Yu
author_sort Hao Zheng
collection DOAJ
description 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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spelling doaj.art-7dc46b8dd26c4e929aa2857d7d3bdb112024-03-05T19:25:37ZengBMCMolecular Medicine1528-36582024-02-0130112310.1186/s10020-024-00788-wRecent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targetsHao Zheng0Yuexuan Liu1Yasi Deng2Yunzhe Li3Shiqi Liu4Yong Yang5Yun Qiu6Bin Li7Wenbing Sheng8Jinzhi Liu9Caiyun Peng10Wei Wang11Huanghe Yu12TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineTCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Innovative Materia Medica Research Institute, Hunan University of Chinese MedicineAbstract 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.https://doi.org/10.1186/s10020-024-00788-wRheumatoid arthritisNFATc1Bone destructionRANKL/RANKOsteoclastOsteoclastogenesis
spellingShingle Hao Zheng
Yuexuan Liu
Yasi Deng
Yunzhe Li
Shiqi Liu
Yong Yang
Yun Qiu
Bin Li
Wenbing Sheng
Jinzhi Liu
Caiyun Peng
Wei Wang
Huanghe Yu
Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets
Molecular Medicine
Rheumatoid arthritis
NFATc1
Bone destruction
RANKL/RANK
Osteoclast
Osteoclastogenesis
title Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets
title_full Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets
title_fullStr Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets
title_full_unstemmed Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets
title_short Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets
title_sort recent advances of nfatc1 in rheumatoid arthritis related bone destruction mechanisms and potential therapeutic targets
topic Rheumatoid arthritis
NFATc1
Bone destruction
RANKL/RANK
Osteoclast
Osteoclastogenesis
url https://doi.org/10.1186/s10020-024-00788-w
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