Quercetin Alleviates Osteoarthritis Pain by Inhibiting Vascular Endothelial Growth Factor A Through Regulating cGAS/STING Pathway

Q: How does quercetin affect pain and inflammation in knee osteoarthritis (KOA) mice?

Quercetin significantly reduces peripheral inflammatory and nociceptive markers, diminishes pain hypersensitivity, and preserves cartilage morphology in KOA mice.

Q: What role does the cGAS/STING pathway play in the study’s mechanism?

The findings link quercetin’s benefits to inhibition of cGAS/STING signaling, which aligns with reduced inflammatory and nociceptive outputs during KOA development.

Q: How is VEGFA/VEGFR1 signaling related to quercetin’s effects?

Quercetin’s suppression of cGAS/STING signaling is accompanied by decreases in VEGFA, VEGFR1, and phosphorylated VEGFR1 levels.

Sep 28, 2026

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Knee osteoarthritis (KOA) is a degenerative joint disease characterized by pain, inflammation, and cartilage degradation, with growing evidence linking it to dysregulated innate immune signaling. This study examines how quercetin modulates the cGAS/STING pathway to regulate pain during KOA progression. Using a mouse model and multiple in vivo and in vitro assays, the work evaluates inflammatory and nociceptive mediators and cartilage integrity, alongside cGAS/STING activity and VEGFA/VEGFR1 signaling changes. Results show quercetin lowers peripheral inflammatory and nociceptive markers, reduces pain hypersensitivity, preserves cartilage morphology, and suppresses VEGFA, VEGFR1, and phosphorylated VEGFR1.

LanguageEnglish

CategoryHealthcare

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Pages16

Reading Time40 min

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Abstract

Introduction

Journal of Cellular and Molecular Medicine ORIGINAL ARTICLE OPEN ACCESS Quercetin Alleviates Osteoarthritis Pain by Inhibiting Vascular Endothelial Growth Factor A Through Regulating cGAS/STING Pathway Enrui Hu1,2,3 | Yibao Wei1,2,3 | Taiyang Liao1,2,3 | Deren Liu1,2,3 | Zijian Gong1,2,3 | Jun Mao1,2 | Peimin Wang1,2 | Nongshan Zhang1,2 1Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China | 2Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu Province, China | 3Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China Correspondence: Nongshan Zhang ([zhangnonhshan@njucm.edu.cn](zhangnonhshan@njucm.edu.cn)) Received: 12 July 2025 | Revised: 18 November 2025 | Accepted: 8 December 2025 Keywords: cGAS/STING | joint pain | knee osteoarthritis | quercetin | VEGFA ABSTRACT Knee osteoarthritis (KOA), a common degenerative joint disease marked by pain, inflammation and cartilage degradation, has been increasingly associated with dysregulated innate immune signalling. Among the implicated molecular pathways, cGAS/ STING has emerged as a key modulator in both disease pathogenesis and therapeutic intervention. Quercetin, a naturally derived bioflavonoid with well-documented antitumour and antioxidant activities, also exerts notable anti-inflammatory and analgesic effects. This study investigated the mechanistic interaction between quercetin and the cGAS/STING pathway in the context of pain regulation throughout KOA development. Forty-eight male C57BL/6J mice were randomly allocated into six groups: Sham, KOA, high-dose quercetin (Que-H), low-dose quercetin (Que-L), STING inhibitor (H-151) and STING activator (SR-717) . Histological evaluations of entire knee joints were performed using haematoxylin and eosin (H&E) and Safranin O/Fast Green (SO&FG) staining protocols. Serum concentrations of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were measured via ELISA. The viability of dorsal root ganglion (DRG) neurons subjected to PGE2 and quercetin was determined through the CCK-8 assay. Expression levels of inflammatory and nociceptive markers were assessed using Western blotting, quantitative PCR, immunofluorescence and immunohistochemistry across both in vivo and in vitro models. Quercetin administration led toa statistically significant reduction in peripheral inflammatory and nociceptive markers (p < 0.05), diminished pain hypersensitivity and preserved cartilage morphology in KOA mice. These outcomes correlated with the inhibition of cGAS/STING signalling and a concomitant decrease in VEGFA, VEGFR1 and phosphorylated VEGFR1 levels (p < 0.05) . By inhibiting the cGAS/ STING signalling pathway, quercetin mitigates KOA-related nociception through the downregulation of VEGFA, VEGFR1 and its phosphorylated form. 1 | Introduction Osteoarthritis (OA) is one of the most widespread and disabling joint disorders, commonly involving the shoulder, hip and knee and often progressing to chronic pain and functional decline [1] . Knee osteoarthritis (KOA), a predominant form of OA, exerts a considerable impact on healthcare systems, socioeconomic stability and overall quality of life [2]. Defined by the progressive breakdown of articular cartilage, subchondral bone remodelling, ligamentous and capsular disruption, synovial inflammation, infrapatellar fat pad alteration, meniscal degeneration, periarticular muscle wasting, fibrotic changes This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. Journal of Cellular and Molec

FAQs

How does quercetin affect pain and inflammation in knee osteoarthritis (KOA) mice?

Quercetin significantly reduces peripheral inflammatory and nociceptive markers, diminishes pain hypersensitivity, and preserves cartilage morphology in KOA mice.

What role does the cGAS/STING pathway play in the study’s mechanism?

The findings link quercetin’s benefits to inhibition of cGAS/STING signaling, which aligns with reduced inflammatory and nociceptive outputs during KOA development.

How is VEGFA/VEGFR1 signaling related to quercetin’s effects?

Quercetin’s suppression of cGAS/STING signaling is accompanied by decreases in VEGFA, VEGFR1, and phosphorylated VEGFR1 levels.

Sep 28, 2026

Uploaded by Well Done