2. Academic Validation
  3. Quercetin Alleviates Osteoarthritis Pain by Inhibiting Vascular Endothelial Growth Factor A Through Regulating cGAS/STING Pathway

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

  • J Cell Mol Med. 2026 Jan;30(1):e70992. doi: 10.1111/jcmm.70992.
Enrui Hu 1 2 3,  Yibao Wei 1 2 3,  Taiyang Liao 1 2 3,  Deren Liu 1 2 3,  Zijian Gong 1 2 3,  Jun Mao 1 2,  Peimin Wang 1 2,  Nongshan Zhang 1 2
Affiliations

Affiliations

  • 1 Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
  • 2 Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu Province, China.
  • 3 Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
PMID: 41474220 DOI: 10.1111/jcmm.70992
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 to a 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.

Keywords

VEGFA; cGAS/STING; joint pain; knee osteoarthritis; quercetin.

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