{
  "abstract": "Background/Objectives: Knee osteoarthritis (KOA) is a major cause of disability, yet the molecular links between extracellular matrix (ECM) remodeling, focal adhesion signaling, and pathological chondrocyte state transitions remain incompletely defined. We aimed to identify focal adhesion-related molecules associated with KOA and characterize their genetic, tissue-level, and single-cell features. Methods: Global Burden of Disease (GBD) 2021 data were used only to provide epidemiologic context for KOA-related disability-adjusted life years (DALYs). Bulk transcriptomic datasets (GSE114007 and GSE169077) were analyzed for differential expression, pathway enrichment, and focal adhesion-related genes. Two-sample Mendelian randomization (MR) integrating blood-derived cis-eQTL summary statistics from eQTLGen with KOA GWAS data was used for exploratory genetic prioritization; these eQTLs were not used as a surrogate measure of cartilage THBS2 expression. THBS2 was further evaluated by expression validation, gene set enrichment, immune-related ssGSEA signature analysis, single-cell RNA sequencing (GSE255460), Slingshot pseudotime analysis, and CellChat. Results: As epidemiologic context, global KOA related DALYs increased from 5.17 million in 1990 to 12.12 million in 2021. Bulk analysis identified 1584 differentially expressed genes (DEGs) and 32 focal adhesion-related candidates. Blood-derived cis-eQTL-based MR showed that genetically instrumented higher THBS2 expression was associated with lower KOA risk (OR = 0.718, 95% CI:0.570-0.905, p = 0.00497), whereas bulk transcriptomic analyses showed higher tissue-level THBS2 expression in KOA cartilage; this bulk difference may reflect both cell-composition changes and cell-intrinsic regulation. Single-cell analysis localized THBS2 mainly to fibrochondrocytes and osteogenic chondrocytes; At the pooled-cell level, THBS2-detectable cells were more frequent in OA than control cartilage (19.45% vs. 1.44%). Pooled CellChat analysis suggested differences in several communication pathways, including higher COLLAGEN, FN1, MIF, LAMININ, and SPP1 pathway scores but a lower THBS pathway score in OA. Conclusions: THBS2 is a genetically prioritized, disease-associated matricellular molecule linked to ECM remodeling and selected disease-associated chondrocyte states in KOA. The CellChat findings describe parallel, broader communication remodeling in the cartilage microenvironment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, 5 JingYuan Road, Shijingshan District, Beijing 100043, China.",
    "Department of Clinical Laboratory, Beijing Shunyi District Hospital, No. 3 Guangming South Street, Shunyi District, Beijing 101300, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gang Hong"
    },
    {
      "affs": [
        0
      ],
      "name": "Baodong Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Le Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaochuan Kong"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiling Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianyi Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lei Zang",
      "orcid": "0000-0003-1403-4159"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ar0rb27e6zq6m.bib",
  "cited_by": 0,
  "doi": "10.3390/genes17101299",
  "fulltext_url": "https://europepmc.org/articles/PMC13704032",
  "id": "ar0rb27e6zq6m",
  "issns": [
    "2073-4425"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938415",
  "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": [
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7222975428",
  "pdf_url": "https://europepmc.org/articles/PMC13704032?pdf=render",
  "pmcid": "PMC13704032",
  "pmid": "42938415",
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ar0rb27e6zq6m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42938415",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938415"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "journal-openalex:1311|Genomics and Rare Diseases",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "THBS2 Marks Disease-Associated Chondrocyte States in Knee Osteoarthritis Cartilage: An Integrative Transcriptomic and Genetic Study.",
  "title_text": "THBS2 Marks Disease-Associated Chondrocyte States in Knee Osteoarthritis Cartilage: An Integrative Transcriptomic and Genetic Study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/ar0rb27e6zq6m",
  "venue": "Genes",
  "versions": []
}