Mechanism of 4-methylcatechol in inhibiting fibroblast-like synoviocyte migration and suppressing inflammatory responses in treatment of rheumatoid arthritis_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

YING Zhendong ¹ , WANG Peng ² , ZHANG Lei ³ , CHEN Dailing ⁴ , WANG Qiuru ⁵ , LIU Qibin ³ , TANG Tiantian ¹ ,  CHEN Changjun ³ ,  MA Qingwei ³

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;

Corresponding author：

CHEN Changjun, Email: Chenchangjun888@qq.com; MA Qingwei, Email: 2605@sdhospital.com.cn

Keywords：

4-methylcatechol; rheumatoid arthritis; fibroblast-like synoviocytes; inflammatory responses; cell migration; mouse

DOI：

10.7507/1002-1892.202503013

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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.

Citation： YING Zhendong, WANG Peng, ZHANG Lei, CHEN Dailing, WANG Qiuru, LIU Qibin, TANG Tiantian, CHEN Changjun, MA Qingwei. Mechanism of 4-methylcatechol in inhibiting fibroblast-like synoviocyte migration and suppressing inflammatory responses in treatment of rheumatoid arthritis. Chinese Journal of Reparative and Reconstructive Surgery, 2025, 39(8): 1051-1060. doi: 10.7507/1002-1892.202503013 Copy

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Chinese Journal of Reparative and Reconstructive Surgery

Mechanism of 4-methylcatechol in inhibiting fibroblast-like synoviocyte migration and suppressing inflammatory responses in treatment of rheumatoid arthritis

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