{
  "abstract": "Distal-less homeobox genes Dlx5 and Dlx6 are key regulators of osteoblast differentiation during skeletal development, but their role in postnatal bone remodeling remains poorly understood. To investigate this, we conditionally deleted Dlx5/6 in Osterix-lineage cells after 4 wk of birth using an inducible Osx-Cre system. Dlx5/6Δ/Δ Osx-Cre and control mice were analyzed in terms of bone architecture (micro-CT), remodeling (histomorphometry), gene expression profiling, and single-cell RNA sequencing. Postnatal deletion of Dlx5/6 induced a complex skeletal phenotype characterized by radial bone hypertrophy and altered cortical remodeling. Enhanced periosteal activity was associated with increased Osx expression in periosteal cells, confirmed by BaseScope and immunofluorescence analyses. In parallel, cortical bone became thinner and more porous, while trabecular bone displayed reduced bone formation and thinner trabeculae, despite paradoxical accumulation within the diaphysis. These alterations were associated with increased Osx expression in periosteal and diaphyseal compartments, indicating abnormal spatial regulation of osteolineage cell expansion and bone remodeling. Single-cell transcriptomic analysis in BM cells identified altered mesenchymal stromal cell populations with dysregulated extracellular matrix and Wnt signaling pathways, including downregulation of the Wnt antagonist Sfrp1, validated in situ by RNAscope. Consistently, osteoblasts derived from Dlx5/6Δ/Δ Osx-Cre displayed impaired terminal differentiation in vitro, with reduced expression of late osteogenic markers and decreased matrix mineralization. Collectively, these findings identify Dlx5/6 as critical regulators of postnatal bone homeostasis that coordinate osteolineage expansion and terminal osteoblast maturation during postnatal bone remodeling.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Morgane Bourmaud"
    },
    {
      "name": "Nicolas Narboux-Neme"
    },
    {
      "name": "Mylène Zarka"
    },
    {
      "name": "Camille Blandin"
    },
    {
      "name": "Sebastien Mella"
    },
    {
      "name": "Valentina Libri"
    },
    {
      "name": "Milena Hasan"
    },
    {
      "name": "Eric Hay"
    },
    {
      "name": "Giovanni Levi"
    },
    {
      "name": "Martine Cohen-Solal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3e9p5kkvj93hw.bib",
  "cited_by": 0,
  "doi": "10.1093/jbmr/zjag112",
  "fulltext_url": null,
  "id": "3e9p5kkvj93hw",
  "issns": [
    "0884-0431",
    "1523-4681"
  ],
  "landing_url": "https://hal.science/hal-05771254v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bc"
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    [
      "openalex",
      "1312|Bone Metabolism and Diseases"
    ]
  ],
  "openalex": "W7169851900",
  "pdf_url": "https://hal.science/hal-05771254/document",
  "pmcid": null,
  "pmid": "42479688",
  "published": "2026-07-21",
  "publisher": "American Society for Bone and Mineral Research",
  "ris": "https://research.draconitic.com/paper/3e9p5kkvj93hw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:44Z",
      "native_id": "hal-05771254",
      "source": "hal",
      "url": "https://hal.science/hal-05771254v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.bc",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.gen",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.mhep",
      "subfield": "general"
    }
  ],
  "title": "Postnatal deletion of Dlx5/6 in Osx-lineage cells drives bone hypertrophy by regulating osteoblast expansion and maturation",
  "title_text": "Postnatal deletion of Dlx5/6 in Osx-lineage cells drives bone hypertrophy by regulating osteoblast expansion and maturation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:44Z",
  "url": "https://research.draconitic.com/paper/3e9p5kkvj93hw",
  "venue": "Journal of Bone and Mineral Research",
  "versions": []
}