isolation-identification-primary-fibroblast-like-synovial-cells-from

Isolation and Identification of Primary Fibroblast-like Synovial Cells from Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial hyperplasia and progressive joint destruction as its ...

Beijing University of Chinese Medicine

China-Japan friendship hospital

This study aims to investigate the therapeutic effect of Wangbi Tablets(WBT) on the inflammation in the rat model of collagen-induced arthritis(CIA) with the syndrome of kidney deficiency based on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway. Eighteen rats were randomly chosen from 24 SPF-grade rats for the modeling of CIA with the syndrome of kidney deficiency. The 24 SPF-grade rats were randomized into 4 groups: control(normal rats), model(CIA with syndrome of kidney deficiency), model+WBT(M+WBT), and model+methotrexate(M+MTX). The syndrome score of kidney deficiency and arthritis index were recorded. The serum levels of interleukin-18(IL-18) and interleukin-1β(IL-1β) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin staining and safranin O-fast green staining were employed to observe the pathological status of ankle joints, synovium, and cartilage. Immunohistochemistry(IHC) was used to detect the expression of polymerase beta(Polβ) and cGAS in rats. The protein levels of polymerase beta(Polβ), cGAS, STING, phospho-STING(p-STING), nuclear factor-kappa B(NF-κB), phospho-NF-κB(p-NF-κB), interferon regulatory factor 3(IRF3), gasdermin-D(GSDMD), GSDMD N-terminus(GSDMD-NT), and cysteinyl aspartate specific proteinase-1(caspase-1) were determined by Western blot. Terminal-deoxynucleoitidyl transferase-mediated dUTP nick end labeling(Tunel) was employed to examine the apoptosis in the articular joints of rats. The results showed that compared with the control group, the model group showed obvious symptoms and signs of kidney deficiency and arthritis. The ankle joint deformity, mental condition, and coat color were improved by WBT. Compared with the model group, WBT alleviated the symptoms and signs of kidney deficiency and arthritis. Compared with the control group, the modeling elevated the serum levels of IL-18 and IL-1β, which were reduced by WBT, especially the level of IL-18. Compared with the control group, the model group showed a large number of inflammatory cells and damage of the cartilage layer in ankle joint, while WBT alleviated the pathological damage. Compared with the control group, the modeling significantly up-regulated the protein levels of cGAS, IRF3, p-NF-κB/NF-κB, caspase-1, and cleaved-caspase-1 and slightly up-regulated the protein levels of p-STING/STING, GSDMD, and GSDMD-NT. Compared with the model group, WBT significantly up-regulated the protein level of Polβ, significantly down-regulated the protein levels of cGAS, IRF3, GSDMD, and GSDMD-NT, and caspase-1, and slightly down-regulated the protein levels of p-STING/STING, p-NF-κB/NF-κB, and cleaved-caspase-1. Compared with the control group, the model group demonstrated decreased apoptosis in the ankle joint, synovium, and neovascularized endothelium, while WBT mitigated these situations. In conclusion, WBT has a therapeutic effect on CIA rats with the syndrome of kidney deficiency. Specifically, WBT may up-regulate the expression of Polβ in the ankle joint and inhibit the cGAS-STING signaling pathway to down-regulate the expression of executive protein of pyroptosis and reduce the release of cytokines, thus inhibiting inflammation and slowing down the progression of bone destruction.

[Wangbi Tablets reduce inflammation in rat model of collagen-induced arthritis with syndrome of kidney deficiency by regulating cGAS-STING signaling pathway].

Osteoarthritis (OA) is a common degenerative joint disease characterized by joint pain, swelling, stiffness, and limited mobility. Current treatments primarily offer partial and short-term relief, with concerns about the potential side effects. This underscores the need for safer and more effective therapeutic strategies. AMP-activated protein kinase (AMPK), a key regulator of cellular energy metabolism, plays an essential role in maintaining the homeostasis of articular cartilage, synovium, and subchondral bone. AMPK signaling has been shown to protect joint tissues from damage caused by mechanical stress and inflammatory responses. Studies suggest that modulating AMPK signaling can influence processes such as autophagy, inflammation, and oxidative stress through downstream targets, including the SIRT family and FoxO family. These mechanisms may help reduce cartilage degradation, osteophyte formation, and synovial inflammation. This review provides a systematic overview of the role of AMPK signaling in joint tissues and explores its potential as a therapeutic target for OA, with the aim of informing the development of targeted therapies that may contribute to more effective and safer management of OA symptoms.

Article	Year
[Wangbi Tablets reduce inflammation in rat model of collagen-induced arthritis with syndrome of kidney deficiency by regulating cGAS-STING signaling pathway]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 39701683	2024
AMPK signaling in osteoarthritis: from mechanisms to targeted therapeutics. Frontiers in pharmacology\| PubMed ID: 41282603	2025

Yu-xin Han

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