{
  "abstract": "Pain severity in osteoarthritis (OA) often dissociates from the extent of cartilage structural damage, indicating that non-structural mechanisms contribute to symptom persistence. Here, we identify articular chondrocytes as active orchestrators of pathological neurovascular invasion through a pathogenic secretome, rather than merely passive victims of degeneration. Integrated human single-cell transcriptomic analysis reveals that OA chondrocytes undergo phenotypic reprogramming characterized by coordinated activation of angiogenic and neurotrophic programs. Functionally, inflammatory chondrocytes directly promote endothelial angiogenesis and sensory axon outgrowth, linking chondrocyte-derived signals to neurovascular invasion and sustained pain. To therapeutically target this upstream mechanism, we engineered MMP-13-responsive celecoxib-loaded hyaluronic acid methacrylate microspheres (HMPC) for disease-adaptive delivery to degenerative cartilage. HMPC suppresses chondrocyte COX-2 activity and remodels the pathological chondrocyte secretome through restoration of miR-339-5p_R-5 and miR-103-3p_R-2, thereby inhibiting angiopoietin-2 (Angpt2)-mediated angiogenesis and brain-derived neurotrophic factor (Bdnf)-driven sensory neurogenesis. In murine OA models, HMPC markedly alleviates pain-related behaviors, reduces neurovascular infiltration, and preserves joint structure. Collectively, this study supports a chondrocyte-centric framework in which reprogrammed chondrocytes govern neurovascular invasion through microRNA-dependent secretome regulation and introduces a smart biomaterial-enabled strategy with disease-modifying potential for OA pain intervention.",
  "abstract_shown": true,
  "affiliations": [
    "Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Basic Medical Sciences, Interdisciplinary Innovation Center for Nanomedicine, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Biomedical Basic Research Center of Jiangsu, Soochow University, Suzhou, Jiangsu, 215000, China.",
    "Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, 570100, China.",
    "Department of Orthopedic Surgery, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu, 214200, China.",
    "Department of Orthopaedics, The Second Affiliated Hospital of Wannan Medical University, Wuhu, Anhui, 241001, China.",
    "Department of Orthopaedic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315000, China.",
    "Sanitation & Environment Technology Institute of Soochow University Ltd, Suzhou, Jiangsu, 215000, China.",
    "Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215123, China.",
    "Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, 215000, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiaonan Yuan"
    },
    {
      "affs": [
        1
      ],
      "name": "Yao Xiao"
    },
    {
      "affs": [
        2
      ],
      "name": "Cheng Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Youzhi Hong"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhen Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiale Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Feng Zhou"
    },
    {
      "affs": [
        4
      ],
      "name": "Liwei Yao"
    },
    {
      "affs": [
        5
      ],
      "name": "Lijie Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Haijiao Mao"
    },
    {
      "affs": [
        0,
        6,
        7
      ],
      "name": "Bin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiaying Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinjin Ma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0s6ddgjp91767.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bioactmat.2026.09.035",
  "fulltext_url": "https://europepmc.org/articles/PMC13677967",
  "id": "0s6ddgjp91767",
  "issns": [
    "2452-199X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42898573",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7221353640",
  "pdf_url": "https://europepmc.org/articles/PMC13677967?pdf=render",
  "pmcid": "PMC13677967",
  "pmid": "42898573",
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0s6ddgjp91767.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42898573",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898573"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "Reprogramming pathological secretory phenotype of chondrocytes inhibits neurovascular invasion for osteoarthritis treatment.",
  "title_text": "Reprogramming pathological secretory phenotype of chondrocytes inhibits neurovascular invasion for osteoarthritis treatment.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/0s6ddgjp91767",
  "venue": "Bioactive materials",
  "versions": []
}