{
  "abstract": "Background\n\nIntervertebral disc degeneration (IDD) is a common degenerative disease and the primary cause of low back pain. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is an activator of the canonical Wnt signaling pathway. But its role in IDD progression and the underlying molecular mechanisms remain poorly understood.Methods\n\nLgr5 knockout (Lgr5 KO) mice were generated by crossing Lgr5flox/flox mice with Prx1-Cre transgenic mice. These samples were analyzed by RNAseq, micro-CT, histology and western blotting, etc.Results\n\nMicroCT analysis of Lgr5 KO and wild-type (WT) mice caudal vertebrae showed that Lgr5 KO mice exhibited narrowed disc space, deteriorated trabecular bone microarchitecture, and decreased bone volume fraction (BV/TV). In a surgically induced IDD model, we showed that Lgr5 KO led to disrupted disc structure, nucleus pulposus (NP) atrophy, cellular loss, and decreased glycosaminoglycan content, thereby accelerating the progression of IDD. RNA-seq analysis identified 900 differentially expressed genes (457 upregulated, 443 downregulated) in Lgr5 KO discs, enriched in osteoclast differentiation, ECM-receptor interaction, and NF-κB signaling pathways. TRAP staining showed enhanced osteoclast activity in Lgr5 KO endplates. Western blot demonstrated reduced Collagen II and increased MMP13, p-p65 in Lgr5 KO NP cells. Immunofluorescence and immunohistochemical staining confirmed that Lgr5 deficiency increased MMP13, p-p65, and Active caspase-3, while decreasing PCNA, promoting inflammation, apoptosis, and suppressing proliferation in NP cells.Conclusions\n\nCollectively, our results demonstrated that Lgr5 deficiency increased inflammation, disrupted ECM homeostasis and NP cell functions, which finally accelerated IDD.",
  "abstract_shown": true,
  "affiliations": [
    "Lingnan Medical Research Center, The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.",
    "College of Artificial Intelligence, Shandong Vocational and Technical University of Engineering, Jinan, China.",
    "School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.",
    "Center for Locomotor System Regenerative Medicine and Technology, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, University Town of Shenzhen, Shenzhen, China.",
    "Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China.",
    "The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Feihong Che"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiangqiang Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiayang Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Guoli Huang"
    },
    {
      "affs": [
        2
      ],
      "name": "Lijuan Yu"
    },
    {
      "affs": [
        3
      ],
      "name": "Gang Li"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Liangliang Xu"
    },
    {
      "affs": [
        5
      ],
      "name": "Ding Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/25ngh85pv1ze0.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1939627",
  "fulltext_url": "https://europepmc.org/articles/PMC13713331",
  "id": "25ngh85pv1ze0",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42952538",
  "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",
      "Original Research"
    ],
    [
      "openalex",
      "2734|Spine and Intervertebral Disc Pathology"
    ]
  ],
  "openalex": "W7221788746",
  "pdf_url": "https://europepmc.org/articles/PMC13713331?pdf=render",
  "pmcid": "PMC13713331",
  "pmid": "42952538",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/25ngh85pv1ze0.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:34Z",
      "native_id": "MED:42952538",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952538"
    },
    {
      "first_seen": "2026-10-31T12:23:54Z",
      "native_id": "PMC13713331",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fmed.2026.1939627"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Spine and Intervertebral Disc Pathology",
      "subfield": "general"
    }
  ],
  "title": "Lgr5 deficiency accelerates intervertebral disc degeneration via NF-κB activation and enhanced osteoclastogenesis.",
  "title_text": "Lgr5 deficiency accelerates intervertebral disc degeneration via NF-κB activation and enhanced osteoclastogenesis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:01Z",
  "url": "https://research.draconitic.com/paper/25ngh85pv1ze0",
  "venue": "Frontiers in medicine",
  "versions": []
}