{
  "abstract": "Osteoarthritis is a whole-joint disease involving articular cartilage, subchondral bone, synovium, vasculature, and peripheral nerves. However, whether joint innervation merely conveys nociceptive input or actively contributes to disease progression remains unresolved. This review integrates evidence on subchondral bone remodeling, synovial inflammation, neurovascular reorganization, and pain sensitization, and proposes a bidirectional neural crosstalk model between subchondral bone and synovium. In subchondral bone, abnormal mechanical loading and osteoclast activation promote sensory nerve ingrowth and neurovascular remodeling through Netrin-1–deleted in colorectal cancer receptor signaling, prostaglandin E2–prostaglandin E receptor 4 signaling, and Slit guidance ligand 3-related pathways. In the synovium, nerve growth factor and inflammatory mediators reinforce sensory sprouting, neuronal excitability, and neuropeptide release. Calcitonin gene-related peptide, substance P, norepinephrine, and neuropeptide Y act on osteoclasts, osteoblast-lineage cells, fibroblast-like synoviocytes, macrophages, and endothelial cells, thereby linking neural activity to bone turnover, synovial immunity, and vascular remodeling. These signals converge on the receptor activator of nuclear factor-κB ligand–osteoprotegerin axis, nuclear factor-κB, and vascular endothelial growth factor-related pathways. Osteochondral channels, periosteal–synovial interfaces, and neurovascular networks may provide anatomical routes for this cross-compartment communication, forming a feedback circuit that sustains structural damage and chronic pain. Neural effects vary across disease stages and tissue compartments, and pain relief does not necessarily confer structural protection. Future therapies should therefore prioritize stage-specific and compartment-selective neuromodulation while assessing pain, function, and joint structural safety in parallel.",
  "abstract_shown": true,
  "affiliations": [
    "Western Sydney University, Sydney, NSW, Australia",
    "Evidence-based Medicine Center, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Luoyang, Henan, China",
    "School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yiran Feng"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Qi Gao"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoya Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yapeng Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4z4ts7t5wx2j3.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1971392",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732130/",
  "id": "4z4ts7t5wx2j3",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://doi.org/10.3389/fmed.2026.1971392",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
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  "openalex": "W7223110834",
  "pdf_url": "https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1971392/pdf",
  "pmcid": "PMC13732130",
  "pmid": "42985373",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4z4ts7t5wx2j3.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:10Z",
      "native_id": "PMC13732130",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fmed.2026.1971392"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "Neural crosstalk between subchondral bone and synovium in osteoarthritis",
  "title_text": "Neural crosstalk between subchondral bone and synovium in osteoarthritis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:10Z",
  "url": "https://research.draconitic.com/paper/4z4ts7t5wx2j3",
  "venue": "Frontiers in Medicine",
  "versions": []
}