Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway.

IF 4.3 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2025-04-28 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1526092

Peng Peng, Wanling Zheng, Yuchen Liu, Jingyuan Huang, Bin Zhang, Jiawei Shen, Jiangang Cao

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引用次数: 0

Abstract

Introduction: Although biomaterials strategies have been regarded as a promising approach for the treatment of osteoarthritis (OA), identifying novel drugs to be delivered for modulate macrophage polarization is still unclear. As a commonly used non-steroidal anti-inflammatory drug for OA, Imrecoxib may be a novel drug to direct and sustain macrophage phenotype. However, the specific protective mechanism of Imrecoxib in OA remains unclear. This study aims to investigate whether Imrecoxib would treat OA by regulating synovial macrophage polarization.

Methods: The research involves constructing mouse destabilization of medial meniscus (DMM) model to assess the changes in pain, bone destruction, cartilage degeneration, and synovial macrophage phenotypes following Imrecoxib treatment. Additionally, the effects of macrophage conditioned medium (CM) pretreated with Imrecoxib on the chondrocyte apoptosis, inflammation and degeneration-related factor expression were evaluated. The role of COX-2/PGE2 signaling pathway in the macrophage phenotype changes was further investigated.

Results: We found that Imrecoxib alleviated pain, cartilage degeneration and synovitis, promoted polarization of M1 macrophages toward M2 phenotype in vivo and in vitro. In vitro experiments, Imrecoxib-CM protected chondrocyte by modulating macrophage polarization. Furthermore, Imrecoxib regulates macrophage polarization through the COX-2/PGE2 pathway.

Conclusion: This study unravels that Imrecoxib protects joint cartilage and attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway, providing new drug delivery strategy for the clinical treatment of OA.

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imrexib通过灭活COX-2/PGE2信号通路，调节滑膜巨噬细胞极化，减轻骨关节炎。

虽然生物材料策略被认为是治疗骨关节炎（OA）的一种很有前途的方法，但确定用于调节巨噬细胞极化的新药仍不清楚。作为OA常用的非甾体类抗炎药，Imrecoxib可能是一种指导和维持巨噬细胞表型的新药。然而，Imrecoxib在OA中的具体保护机制尚不清楚。本研究旨在探讨Imrecoxib是否通过调节滑膜巨噬细胞极化来治疗OA。方法：建立小鼠内侧半月板不稳定（DMM）模型，评估imrexib治疗后疼痛、骨破坏、软骨变性和滑膜巨噬细胞表型的变化。此外，我们还评估了Imrecoxib预处理巨噬细胞条件培养基（macrophage conditioned medium， CM）对软骨细胞凋亡、炎症和变性相关因子表达的影响。进一步研究COX-2/PGE2信号通路在巨噬细胞表型改变中的作用。结果：我们发现Imrecoxib在体内和体外均能减轻疼痛、软骨退变和滑膜炎，促进M1巨噬细胞向M2表型极化。在体外实验中，Imrecoxib-CM通过调节巨噬细胞极化来保护软骨细胞。此外，Imrecoxib通过COX-2/PGE2途径调节巨噬细胞极化。结论：本研究揭示了Imrecoxib通过灭活COX-2/PGE2信号通路，调节滑膜巨噬细胞极化，保护关节软骨，减轻骨关节炎，为临床治疗OA提供了新的给药策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.