{
  "abstract": "Bone morphogenetic protein 2 (BMP2) has the potential to drive multipotent mesenchymal stem cells (MSCs) to undergo chondral-osteogenic (including hypertrophic chondrocyte) differentiation. Parathyroid hormone-related protein (PTHrP) plays an essential role in fetal endochondral ossification, although persistent PTHrP stimulation leads to postnatal bone loss. Here, we investigated the effects of PTHrP on BMP2-induced endochondral ossification through hypertrophic chondrocyte differentiation of MSCs. We found that silencing PTHrP expression inhibited BMP2-induced chondrogenic, hypertrophic, and osteogenic differentiation of MSCs, while overexpression of PTHrP promoted BMP2-induced chondrogenic differentiation of MSCs and suppressed BMP2-induced hypertrophic differentiation of MSCs. Using stem cell implantation studies in athymic nude mice, we demonstrated that while MSCs with silenced PTHrP expression exhibited significantly reduced endochondral ossification of subcutaneous cartilage, overexpression of PTHrP promoted the growth of subcutaneous cartilage while significantly delaying ossification, leading to the preservation of cartilage phenotype. Mechanistically, we showed that exogenous PTHrP promoted BMP2-induced chondrogenic differentiation of MSCs by up-regulating Sox9 expression and inactivating PI3K-AKT signaling. Collectively, our findings strongly suggest that PTHrP may play an important role in mediating BMP2-induced chondral-osteogenic differentiation of MSCs by inactivating PI3K-AKT signaling, indicating that PTHrP may be exploited for endochondral cartilage-bone tissue engineering.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopaedic Surgery, Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine, Orthopaedic Research Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.",
    "Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago, Medical Center, Chicago, IL 60637, USA.",
    "Medical Examination Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.",
    "Department of Orthopaedic Surgery, The Second People's Hospital of Chongqing Yubei District, Chongqing 401147, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shengqiang Gao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Piao Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Tingting Du"
    },
    {
      "affs": [
        3
      ],
      "name": "Yu Ye"
    },
    {
      "affs": [
        0
      ],
      "name": "Shengwen Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Senrui Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chengcheng Du"
    },
    {
      "affs": [
        1
      ],
      "name": "Tong-Chuan He"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhenglin Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Junyi Liao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ees6ke2pm48x.bib",
  "cited_by": 0,
  "doi": "10.1016/j.gendis.2026.102273",
  "fulltext_url": "https://europepmc.org/articles/PMC13694792",
  "id": "5ees6ke2pm48x",
  "issns": [
    "2352-4820",
    "2352-3042"
  ],
  "landing_url": "https://europepmc.org/article/MED/42926813",
  "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": [
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7163649734",
  "pdf_url": "https://europepmc.org/articles/PMC13694792?pdf=render",
  "pmcid": "PMC13694792",
  "pmid": "42926813",
  "published": "2026-06-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5ees6ke2pm48x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:20Z",
      "native_id": "MED:42926813",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42926813"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "PTHrP suppresses BMP2-induced osteochondral differentiation and preserves cartilage phenotype in mesenchymal stem cells via inactivating PI3K-AKT signaling.",
  "title_text": "PTHrP suppresses BMP2-induced osteochondral differentiation and preserves cartilage phenotype in mesenchymal stem cells via inactivating PI3K-AKT signaling.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:20Z",
  "url": "https://research.draconitic.com/paper/5ees6ke2pm48x",
  "venue": "Genes & diseases",
  "versions": []
}