{
  "abstract": "Estrogen deficiency disrupts the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, resulting in progressive bone loss. Although AMP-activated protein kinase (AMPK) regulates the differentiation and activity of both skeletal cell lineages, the role of endogenous purine metabolites in this process remains poorly understood. We investigated adenine responses and AMPK-associated signaling in skeletal-cell models and assessed histological and protein changes in ovariectomized (OVX) mice. In C2C12 cells and primary bone marrow-derived mesenchymal stem/stromal cells, adenine increased AMPK and cAMP response element-binding protein phosphorylation; upregulated runt-related transcription factor 2, alkaline phosphatase, collagen I, and osteopontin; and enhanced alkaline phosphatase staining and matrix mineralization. In C2C12 cells, Compound C and AMPKα knockdown attenuated these osteogenic responses. In receptor activator of nuclear factor-κB ligand-stimulated RAW264.7 cells and bone marrow-derived macrophages, adenine increased AMPK phosphorylation and reduced osteoclastogenic signaling, tartrate-resistant acid phosphatase staining, and cathepsin K expression. Responses to adenine remained detectable after AMPKα knockdown in RAW264.7 cells. In OVX mice, dietary supplementation with 0.02% adenine for 10 weeks was associated with increased histology-derived trabecular thickness and bone area fraction and changes in bone-associated protein expression. No significant differences were detected in the assessed renal and hepatic indices. These findings support further preclinical investigation of adenine in estrogen-deficiency bone loss.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University Busan 46241 Republic of Korea",
    "Environmental Safety Group, KIST Europe Forschungsgesellschaft mbH, Saarbrücken 66123 Germany",
    "College of Pharmacy, Jeju Research Institute of Pharmaceutical Sciences, Jeju National University, Jeju 63243 Yangsan 50612 Republic of Korea",
    "Department of Biomedical Laboratory Science, Daejeon Institute of Science and Technology, Daejeon 35408 Yangsan 50612 Republic of Korea",
    "College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826 Yangsan 50612 Republic of Korea",
    "Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital Yangsan 50612 Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "RanJu Woo"
    },
    {
      "affs": [
        1
      ],
      "name": "Chang Seon Ryu"
    },
    {
      "affs": [
        2
      ],
      "name": "Doyoung Kwon"
    },
    {
      "affs": [
        0
      ],
      "name": "Sou Hyun Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Ki Wung Chung"
    },
    {
      "affs": [
        0
      ],
      "name": "Jaewon Lee"
    },
    {
      "affs": [
        3
      ],
      "name": "Keuk-Jun Kim"
    },
    {
      "affs": [
        4
      ],
      "name": "Yun-Hee Lee"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Young-Suk Jung"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ahrhsf9evk1p.bib",
  "cited_by": 0,
  "doi": "10.4062/biomolther.2026.201",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728447/",
  "id": "5ahrhsf9evk1p",
  "issns": [
    "1976-9148",
    "2005-4483"
  ],
  "landing_url": "https://doi.org/10.4062/biomolther.2026.201",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Bone Metabolism and Diseases"
    ]
  ],
  "openalex": "W7224391417",
  "pdf_url": "https://www.biomolther.org/journal/download_pdf.php?doi=10.4062/biomolther.2026.201",
  "pmcid": "PMC13728447",
  "pmid": "42952217",
  "published": "2026-11-01",
  "publisher": "Korean Society of Applied Pharmacology",
  "ris": "https://research.draconitic.com/paper/5ahrhsf9evk1p.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:21:26Z",
      "native_id": "PMC13728447",
      "source": "pmc",
      "url": "https://doi.org/10.4062/biomolther.2026.201"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Bone Metabolism and Diseases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Adenine Promotes Osteogenic Differentiation and Suppresses Osteoclastogenesis",
  "title_text": "Adenine Promotes Osteogenic Differentiation and Suppresses Osteoclastogenesis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:26Z",
  "url": "https://research.draconitic.com/paper/5ahrhsf9evk1p",
  "venue": "Biomolecules & Therapeutics",
  "versions": []
}