ArticlePloS one2010
The ARF tumor suppressor regulates bone remodeling and osteosarcoma development in mice.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Genetically Modified Mouse Models for Sarcoma Research: A Comprehensive Review.Current oncology reports · 2025Review
- A Review of Signaling Transduction Mechanisms in Osteoclastogenesis Regulation by Autophagy, Inflammation, and Immunity.International journal of molecular sciences · 2022Review
- Mast4 determines the cell fate of MSCs for bone and cartilage development.Nature communications · 2022Article
- TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development.Frontiers in cell and developmental biology · 2021Article
- Root resorption and ensuing cementum repair by Wnt/β-catenin dependent mechanism.American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics · 2020Article
- IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice.International journal of oral science · 2020Article
- A Correlation between Wnt/Beta-catenin Signaling and the Rate of Dentin Secretion.Journal of endodontics · 2019Article
- Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation.Journal of visualized experiments : JoVE · 2016Article
- Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma.Cancer letters · 2016Review
- WIP1 deficiency inhibits HTLV-1 Tax oncogenesis: novel therapeutic prospects for treatment of ATL?Retrovirology · 2012Article
- Mouse models of sarcomas: critical tools in our understanding of the pathobiology.Clinical sarcoma research · 2012Article
- Genetically engineered mouse models and human osteosarcoma.Clinical sarcoma research · 2012Article
- New mouse models for metabolic bone diseases generated by genome-wide ENU mutagenesis.Mammalian genome : official journal of the International Mammalian Genome Society · 2012Article
- CD8+ T cells regulate bone tumor burden independent of osteoclast resorption.Cancer research · 2011Article
- Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The ARF tumor suppressor regulates p53 as well as basic developmental processes independent of p53, including osteoclast activation, by controlling ribosomal biogenesis. Here we provide evidence that ARF is a master regulator of bone remodeling and osteosarcoma (OS) development in mice. Arf(-/-) mice displayed increased osteoblast (OB) and osteoclast (OC) activity with a significant net increase in trabecular bone volume. The long bones of Arf(-/-) mice had increased expression of OB genes while Arf(-/-) OB showed enhanced differentiation in vitro. Mice transgenic for the Tax oncogene develop lymphocytic tumors with associated osteolytic lesions, while Tax+Arf(-/-) mice uniformly developed spontaneous OS by 7 months of age. Tax+Arf(-/-) tumors were well differentiated OS characterized by an abundance of new bone with OC recruitment, expressed OB markers and displayed intact levels of p53 mRNA and reduced Rb transcript levels. Cell lines established from OS recapitulated characteristics of the primary tumor, including the expression of mature OB markers and ability to form mineralized tumors when transplanted. Loss of heterozygosity in OS tumors arising in Tax+Arf(+/-) mice emphasized the necessity of ARF-loss in OS development. Hypothesizing that inhibition of ARF-regulated bone remodeling would repress development of OS, we demonstrated that treatment of Tax+Arf(-/-) mice with zoledronic acid, a bisphosphonate inhibitor of OC activity and repressor of bone turnover, prevented or delayed the onset of OS. These data describe a novel role for ARF as a regulator of bone remodeling through effects on both OB and OC. Finally, these data underscore the potential of targeting bone remodeling as adjuvant therapy or in patients with genetic predispositions to prevent the development of OS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.