{
  "abstract": "Epigallocatechin-3-gallate (EGCG), the principal catechin of green tea, exhibits broad anti-inflammatory properties; however, its effect on protease-activated receptor-2 (PAR-2)–mediated signaling in osteoarthritis (OA) has not been investigated. Here, we report that EGCG (5–10 µM) dose-dependently suppresses PAR-2 expression at both mRNA and protein levels in lipopolysaccharide (LPS)-stimulated human chondrocytes derived from bone marrow mesenchymal stem cells. This upstream inhibition attenuated ERK1/2 phosphorylation (pERK/total ERK ratio reduced below basal levels at 10 µM) and produced concordant suppression of three functionally linked effector arms: (i) pro-inflammatory cytokines (TNF-α, IL-1β, MCP-1), with near-maximal inhibition at 10 µM and a saturation plateau at 20 µM; (ii) the SOX4–ADAMTS-5 catabolic axis (81.9% and 66.2% protein reduction, respectively); and (iii) RANK/RANKL surface expression. EGCG also restored mitochondrial membrane potential and biomass to near-homeostatic levels. Crucially, small interfering RNA (siRNA)-mediated PAR-2 silencing reduced LPS-induced TNF-α by ~38% and substantially blunted EGCG’s incremental efficacy, supporting PAR-2 as a predominant, though not exclusive, mediator of EGCG’s anti-inflammatory action. The effective concentrations employed are physiologically attainable through dietary green tea consumption, as documented by a comprehensive survey of EGCG content across 36 commercial varieties. These findings support PAR-2 as a candidate upstream target of EGCG in OA chondrocytes and suggest a mechanistic model involving PAR-2 → ERK1/2 → TNF-α/SOX4/ADAMTS-5, through which a dietary polyphenol exerts coordinated anti-inflammatory and anti-catabolic effects, while preserving structural and thermodynamic markers of mitochondrial integrity.",
  "abstract_shown": true,
  "affiliations": [
    "College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, United Arab Emirates."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rajashree Patnaik"
    },
    {
      "affs": [
        0
      ],
      "name": "Yajnavalka Banerjee",
      "orcid": "0000-0002-7546-8893"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/46w8e89dg5ata.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0357766",
  "fulltext_url": "https://europepmc.org/articles/PMC13726950",
  "id": "46w8e89dg5ata",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0357766",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Anatomy"
    ],
    [
      "heading",
      "Animal Cells"
    ],
    [
      "heading",
      "Arthritis"
    ],
    [
      "heading",
      "Beverages"
    ],
    [
      "heading",
      "Biochemistry"
    ],
    [
      "heading",
      "Bioenergetics"
    ],
    [
      "heading",
      "Biological Tissue"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Cartilage"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "heading",
      "Cellular Structures and Organelles"
    ],
    [
      "heading",
      "Cellular Types"
    ],
    [
      "heading",
      "Chondrocytes"
    ],
    [
      "heading",
      "Clinical Medicine"
    ],
    [
      "heading",
      "Connective Tissue"
    ],
    [
      "heading",
      "Connective Tissue Cells"
    ],
    [
      "heading",
      "Cytokines"
    ],
    [
      "heading",
      "Developmental Biology"
    ],
    [
      "heading",
      "Diet"
    ],
    [
      "heading",
      "Energy-Producing Organelles"
    ],
    [
      "heading",
      "Gene Expression"
    ],
    [
      "heading",
      "Genetics"
    ],
    [
      "heading",
      "Immune Physiology"
    ],
    [
      "heading",
      "Immune Response"
    ],
    [
      "heading",
      "Immune System"
    ],
    [
      "heading",
      "Immunology"
    ],
    [
      "heading",
      "Inflammation"
    ],
    [
      "heading",
      "Innate Immune System"
    ],
    [
      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Mitochondria"
    ],
    [
      "heading",
      "Molecular Development"
    ],
    [
      "heading",
      "Nutrition"
    ],
    [
      "heading",
      "Osteoarthritis"
    ],
    [
      "heading",
      "Physiology"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Rheumatology"
    ],
    [
      "heading",
      "Signs and Symptoms"
    ],
    [
      "heading",
      "Tea"
    ],
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Cartilage"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Cartilage/Chondrocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Chondrocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Musculoskeletal system/Skeleton/Skeletal joints"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Bioenergetics/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Regulatory proteins/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Connective tissue cells/Chondrocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Biology and life sciences/Nutrition/Diet/Beverages/Tea"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Cartilage"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Cartilage/Chondrocytes"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Chondrocytes"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Musculoskeletal system/Skeleton/Skeletal joints"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Nutrition/Diet/Beverages/Tea"
    ],
    [
      "plos",
      "/Medicine and health sciences/Rheumatology/Arthritis/Osteoarthritis"
    ]
  ],
  "openalex": "W7225099794",
  "pdf_url": "https://europepmc.org/articles/PMC13726950?pdf=render",
  "pmcid": "PMC13726950",
  "pmid": "42970575",
  "published": "2026-11-02",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/46w8e89dg5ata.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:20:16Z",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Gene Expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "heading:Cell Biology",
      "subfield": "cell-biology"
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    {
      "field": "biology",
      "origin": "heading:Developmental Biology",
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      "origin": "heading:Genetics",
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  ],
  "title": "Epigallocatechin-3-gallate attenuates PAR-2–mediated inflammatory signaling and preserves markers of mitochondrial integrity in osteoarthritic chondrocytes",
  "title_text": "Epigallocatechin-3-gallate attenuates PAR-2–mediated inflammatory signaling and preserves markers of mitochondrial integrity in osteoarthritic chondrocytes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:46Z",
  "url": "https://research.draconitic.com/paper/46w8e89dg5ata",
  "venue": "PLOS One",
  "versions": []
}