Synergistic therapeutic effect of parecoxib and ilomastat combination in osteoarthritis via inhibition of IL-17/PI3K/AKT/NF-κB activity

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2025-02-10 DOI:10.1016/j.molimm.2025.02.005

Xiaofei Feng , Yao Ma , Yuhao Zhao , Zhenrui Zhao , Zhengdong Song , Li Lin , Wenji Wang

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引用次数: 0

Abstract

Background

Osteoarthritis is a degenerative disease, and current drug treatment is to give nonsteroidal anti-inflammatory drugs to relieve symptoms. The anti-inflammatory ability of parecoxib and ilomastat has been confirmed, but the synergistic effect of combined administration in osteoarthritis has not been clear.

Methods

Mouse primary chondrocytes stimulated with IL-1β were cultured. The expression levels of inflammatory cytokines and matrix metalloproteinases were investigated by western blotting, quantitative real-time polymerase chain reaction and ELISA. The effects of parecoxib and ilomastat on chondrocyte apoptosis were evaluated by flow cytometry. In addition, the rat model of osteoarthritis was established by meniscal instability, and the morphological changes of cartilage and the expression levels of related molecules were monitored using Safranin O-Fast green and immunohistochemical staining after intra-articular injection of parecoxib, ilomastat, and the combination of the two.

Results

In vitro experiments showed that the combined administration of parecoxib and ilomastat more effectively inhibited the expression of proinflammatory factors and matrix metalloproteinases compared with single drug administration. The combined drug treatment could more effectively inhibit IL-1β-induced chondrocyte apoptosis. The combined drug treatment alleviated the progression of osteoarthritis by inhibiting the IL-17/PI3K/AKT/NF-κB pathway. In addition, in vivo experiments showed that the combined administration could improve the further deterioration of the osteoarthritis rat model.

Conclusions

The combined administration of parecoxib and ilomastat to inhibit IL-17/PI3K/AKT/NF-κB transduction is beneficial to reduce the infiltration of inflammatory factors and matrix metalloproteinases in osteoarthritis.

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.