{
  "abstract": "Poly (ADP-ribose) glycohydrolase (PARG) is the main enzyme responsible for degrading poly (ADP-ribose) (PAR), which is synthesized by PARP family proteins during the poly ADP-ribosylation cycle. We previously reported that the PARG inhibitor PDD00017273 suppressed osteoclast differentiation through PAR accumulation in RANKL-stimulated RAW264 cells. However, the molecular mechanisms of osteoclast differentiation under PARG inhibition remain unclear, and elucidation of the regulatory mechanisms may contribute to the development of novel therapeutic strategies for metabolic bone diseases associated with excessive activation of osteoclasts. In the present study, we investigated the molecular mechanisms whereby PDD00017273 suppresses osteoclast differentiation. RNA-seq and pathway analyses revealed enrichment of oxidative stress- and redox regulation-related pathways, and an ATAC-seq analysis identified enrichment of the NRF2-binding motif in PDD00017273-treated RAW264 cells compared with DMSO-treated control cells. Pharmacological inhibition of NRF2 partially restored the osteoclast formation suppressed by PDD00017273. Under these conditions, the expression levels of NRF2-regulated genes were suppressed, while the expression levels of osteoclast marker genes were upregulated. Taken together, the present findings suggest that PAR accumulation via PARG inhibition suppresses osteoclast differentiation through NRF2 activation, indicating that PAR metabolism plays an important role in osteoclast differentiation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology, School of Dentistry, Osaka Dental University, Hirakata, Osaka, Japan",
    "Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuka Sasaki"
    },
    {
      "affs": [
        1
      ],
      "name": "Ryusuke Nakatsuka"
    },
    {
      "name": "Ryoji Taniguchi"
    },
    {
      "name": "Amane Inoue"
    },
    {
      "name": "Mitsuko Masutani"
    },
    {
      "name": "Tadashige Nozaki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7f5w0aradb76m.bib",
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  "doi": "10.1371/journal.pone.0361101",
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  "id": "7f5w0aradb76m",
  "issns": [
    "1932-6203"
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  "landing_url": "https://doi.org/10.1371/journal.pone.0361101",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Bone Metabolism and Diseases"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Bone/Osteoclasts"
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      "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Osteoclasts"
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      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Connective tissue cells/Osteoclasts"
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    [
      "plos",
      "/Biology and life sciences/Cell biology/Chromosome biology/Chromatin"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Cell differentiation"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Cell differentiation/Osteoblast differentiation"
    ],
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      "plos",
      "/Biology and life sciences/Genetics/Epigenetics/Chromatin"
    ],
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      "/Biology and life sciences/Genetics/Gene expression"
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      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Chromatin"
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      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcriptional control"
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    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Bone remodeling"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Bone/Osteoclasts"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Osteoclasts"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Musculoskeletal system/Skeleton/Bone/Osteoclasts"
    ]
  ],
  "openalex": "W7223706963",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0361101&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/7f5w0aradb76m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.1371/journal.pone.0361101",
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      "url": "https://doi.org/10.1371/journal.pone.0361101"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  "title": "PARG inhibition suppresses osteoclast differentiation through transcriptional activation of an NRF2-dependent pathway",
  "title_text": "PARG inhibition suppresses osteoclast differentiation through transcriptional activation of an NRF2-dependent pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/7f5w0aradb76m",
  "venue": "PLOS One",
  "versions": []
}