Mechanism of 4-methylcatechol in inhibiting fibroblast-like synoviocyte migration and suppressing inflammatory responses in treatment of rheumatoid arthritis.
10.7507/1002-1892.202503013
- Author:
Zhendong YING
1
;
Peng WANG
2
;
Lei ZHANG
3
;
Dailing CHEN
4
;
Qiuru WANG
5
;
Qibin LIU
3
;
Tiantian TANG
1
;
Changjun CHEN
3
;
Qingwei MA
3
Author Information
1. Department of Orthopaedics, Shandong Provincial Qianfoshan Hospital, Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan Shandong, 250012, P. R. China.
2. Department of Orthopaedics, the Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan Shandong, 250031, P. R. China.
3. Department of Orthopaedics, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan Shandong, 250012, P. R. China.
4. Department of Orthopaedics, Shandong Provincial Qianfoshan Hospital, Shandong Second Medical University, Jinan Shandong, 250012, P. R. China.
5. Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China.
- Publication Type:Journal Article
- Keywords:
4-methylcatechol;
cell migration;
fibroblast-like synoviocytes;
inflammatory responses;
mouse;
rheumatoid arthritis
- MeSH:
Synoviocytes/metabolism*;
Arthritis, Rheumatoid/metabolism*;
Animals;
Cell Movement/drug effects*;
Humans;
Catechols/therapeutic use*;
Fibroblasts/drug effects*;
Mice;
Tumor Necrosis Factor-alpha/pharmacology*;
Interleukin-1beta/metabolism*;
Interleukin-6/metabolism*;
Signal Transduction/drug effects*;
NF-kappa B/metabolism*;
Transcription Factor RelA/metabolism*;
Synovial Membrane/cytology*;
Cells, Cultured;
Male;
Arthritis, Experimental;
Anti-Inflammatory Agents/pharmacology*;
NF-KappaB Inhibitor alpha;
Inflammation
- From:
Chinese Journal of Reparative and Reconstructive Surgery
2025;39(8):1051-1060
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action.
METHODS:RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination.
RESULTS:4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice.
CONCLUSION:4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
