{
  "abstract": "Introduction: Tristetraprolin (TTP) is an RNA-binding protein essential for controlling cytokine production, and its deficiency leads to profound skeletal deterioration. Although TTP deficiency is associated with systemic inflammation and microbial dysbiosis, the contribution of the gut microbiota to bone pathology remains poorly defined.\n\nMaterials and methods: We investigated whether the microbiome causally modulates osteoimmune mechanisms and bone microarchitecture in TTP-deficient mice. To isolate the effects of the microbiome, we utilized specific pathogen-free (SPF) and germ-free (GF) co-housing mouse models.\n\nResults: Microbial transfer bidirectionally regulated systemic inflammation and the expansion of monocytic myeloid-derived suppressor cells (M-MDSCs), a population with potent osteoclastogenic capacity. Importantly, microbiota transfer was sufficient to induce osteoclast activation and a selective deterioration of trabecular bone microarchitecture in otherwise healthy mice, without affecting overall bone mass. Crucially, the transmission of these osteoimmune and skeletal phenotypes was microbiota-dependent; while a baseline genetic bone deficit persisted in GF TTP-deficient mice, the co-housing-induced M-MDSC expansion and trabecular bone alterations were not observed under GF conditions.\n\nConclusion: Our findings identify a microbiota-dependent osteoimmune axis that amplifies inflammatory bone loss in TTP deficiency. This work establishes the gut microbiome as a mechanistic modifier of bone quality in genetically driven inflammatory disease and highlights microbial targeting as a potential therapeutic strategy for inflammatory bone loss.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00774-026-01753-9.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oral Microbiology, College of Dentistry, Kyung Hee University, Seoul, South Korea",
    "Department of Oral Biology, State University of New York at Buffalo, University at Buffalo, Buffalo, NY USA",
    "Division of Digestive and Liver DiseasesDepartment of Medicine, University of Texas Southwestern Medical Center, Dallas, TX USA",
    "Molecular and Cellular Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC USA",
    "Departments of Biochemistry & Medicine, Duke University Medical Center, Durham, NC USA",
    "Department of Oral Biology, School of Dental Medicine, University at Buffalo, 645 Biomedical Research Building, 3435 Main St, Buffalo, NY USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kyu Hwan Kwack"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jiho Sohn"
    },
    {
      "affs": [
        1
      ],
      "name": "Lixia Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Lu Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Reegan Mullaney"
    },
    {
      "affs": [
        3
      ],
      "name": "Yukitomo Arao"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Perry J. Blackshear"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Keith L. Kirkwood",
      "orcid": "0000-0003-4519-8973"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e58tqjxmmtabv.bib",
  "cited_by": 0,
  "doi": "10.1007/s00774-026-01753-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723533/",
  "id": "e58tqjxmmtabv",
  "issns": [
    "0914-8779",
    "1435-5604"
  ],
  "landing_url": "https://doi.org/10.1007/s00774-026-01753-9",
  "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",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Bone Metabolism and Diseases"
    ]
  ],
  "openalex": "W7203630783",
  "pdf_url": null,
  "pmcid": "PMC13723533",
  "pmid": "42606596",
  "published": "2026-08-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e58tqjxmmtabv.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:09Z",
      "native_id": "PMC13723533",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00774-026-01753-9"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Bone Metabolism and Diseases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Gut microbiota transmits osteoimmune dysregulation and exacerbates trabecular bone loss in tristetraprolin-deficient mice",
  "title_text": "Gut microbiota transmits osteoimmune dysregulation and exacerbates trabecular bone loss in tristetraprolin-deficient mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:20Z",
  "url": "https://research.draconitic.com/paper/e58tqjxmmtabv",
  "venue": "Journal of Bone and Mineral Metabolism",
  "versions": []
}