Nitazoxanide reduces inflammation and bone erosion in mice with collagen-induced arthritis via inhibiting the JAK2/STAT3 and NF-κB pathways in fibroblast-like synoviocytes
Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved..
Our recent study showed that Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, prevents ovariectomy-induced bone loss by inhibiting osteoclast activity. However, there have been no investigations to determine whether NTZ has preventive potential in other bone resorbing diseases, especially rheumatoid arthritis (RA). In this study, the primary RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) murine model were used to evaluate the effect of NTZ. The results showed that NTZ potently inhibited proliferation, migration and invasion capacity of RA-FLS in a dose dependent manner by restraining cell entry into S phases, without induction of cell apoptosis. NTZ obviously reduced spontaneous mRNA expression of IL-1β, IL-6 and RANKL, as well as TNF-α-induced transcription of the IL-1β, IL-6, and MMP9 genes. In terms of molecular mechanism, NTZ significantly inhibited the basal or TNF-α-induced activation of JAK2/STAT3 (T705) and NF-κB pathway, but not MAPK and STAT3 (S727) phosphorylation. Moreover, NTZ ameliorated synovial inflammation and bone erosion in CIA mice through reducing the production of inflammatory mediators and osteoclast formation, respectively. Collectively, our findings indicate that NTZ exhibits anti-inflammatory and anti-erosive effects both ex vivo and in vivo, which provides promising evidence for the therapeutic application of NTZ as a novel therapeutic agent for RA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:171 |
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| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 171(2024) vom: 08. Feb., Seite 116195 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Changhong [VerfasserIn] |
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| Links: |
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| Themen: |
Bone erosion |
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| Anmerkungen: |
Date Completed 08.02.2024 Date Revised 08.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biopha.2024.116195 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Our recent study showed that Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, prevents ovariectomy-induced bone loss by inhibiting osteoclast activity. However, there have been no investigations to determine whether NTZ has preventive potential in other bone resorbing diseases, especially rheumatoid arthritis (RA). In this study, the primary RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) murine model were used to evaluate the effect of NTZ. The results showed that NTZ potently inhibited proliferation, migration and invasion capacity of RA-FLS in a dose dependent manner by restraining cell entry into S phases, without induction of cell apoptosis. NTZ obviously reduced spontaneous mRNA expression of IL-1β, IL-6 and RANKL, as well as TNF-α-induced transcription of the IL-1β, IL-6, and MMP9 genes. In terms of molecular mechanism, NTZ significantly inhibited the basal or TNF-α-induced activation of JAK2/STAT3 (T705) and NF-κB pathway, but not MAPK and STAT3 (S727) phosphorylation. Moreover, NTZ ameliorated synovial inflammation and bone erosion in CIA mice through reducing the production of inflammatory mediators and osteoclast formation, respectively. Collectively, our findings indicate that NTZ exhibits anti-inflammatory and anti-erosive effects both ex vivo and in vivo, which provides promising evidence for the therapeutic application of NTZ as a novel therapeutic agent for RA | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Inflammation | |
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| 650 | 4 | |a Nitazoxanide | |
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| 700 | 1 | |a Han, Yijun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhai, Jiayu |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Yinji |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Zhongqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jinxia |e verfasserin |4 aut | |
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