ArticleMolecular cancer research : MCR2008
The retinoblastoma protein tumor suppressor is important for appropriate osteoblast differentiation and bone development.
Article in Molecular cancer research : MCR, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 76 citations in OpenAlex.
- Loss of Function of the Retinoblastoma Gene Affects Gap Junctional Intercellular Communication and Cell Fate in Osteoblasts.Biology · 2024Article
- Review
- Targeting RNA Polymerase I Transcription Activity in Osteosarcoma: Pre-Clinical Molecular and Animal Treatment Studies.Biomedicines · 2023Article
- Transcriptional Repression by FoxM1 Suppresses Tumor Differentiation and Promotes Metastasis of Breast Cancer.Cancer research · 2022Article
- Improvement of quality of life by conservative management of thoracic scoliosis at 172°: a case report.Journal of medicine and life · 2022Article
- Investigation of the role of the miR17-92 cluster in BMP9-induced osteoblast lineage commitment.Journal of orthopaedic surgery and research · 2021Article
- ASCL1 represses a SOX9Genes & development · 2021Article
- Pickle Recruits Retinoblastoma Related 1 to Control Lateral Root Formation inInternational journal of molecular sciences · 2021Article
- Effects of Cellular Senescence on Dental Follicle Cells.Pharmacology · 2021Review
- The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development.Nutrients · 2020Article
- EZH2 reduction is an essential mechanoresponse for the maintenance of super-enhancer polarization against compressive stress in human periodontal ligament stem cells.Cell death & disease · 2020Article
- p21BMC musculoskeletal disorders · 2017Article
- Improvement of gemcitabine sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells by RUNX2 depletion-mediated augmentation of TAp73-dependent cell death.Oncogenesis · 2016Article
- The human ARF tumor suppressor senses blastema activity and suppresses epimorphic tissue regeneration.eLife · 2015Article
- Signaling pathways involved in megakaryocyte-mediated proliferation of osteoblast lineage cells.Journal of cellular physiology · 2015Article
- Article
- Article
- Loss of pRB and p107 disrupts cartilage development and promotes enchondroma formation.Oncogene · 2013Article
- Article
- Perspectives on cancer stem cells in osteosarcoma.Cancer letters · 2013Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mutation of the retinoblastoma (RB) tumor suppressor gene is strongly linked to osteosarcoma formation. This observation and the documented interaction between the retinoblastoma protein (pRb) and Runx2 suggests that pRb is important in bone development. To assess this hypothesis, we used a conditional knockout strategy to generate pRb-deficient embryos that survive to birth. Analysis of these embryos shows that Rb inactivation causes the abnormal development and impaired ossification of several bones, correlating with an impairment in osteoblast differentiation. We further show that Rb inactivation acts to promote osteoblast differentiation in vitro and, through conditional analysis, establish that this occurs in a cell-intrinsic manner. Although these in vivo and in vitro differentiation phenotypes seem paradoxical, we find that Rb-deficient osteoblasts have an impaired ability to exit the cell cycle both in vivo and in vitro that can explain the observed differentiation defects. Consistent with this observation, we show that the cell cycle and the bone defects in Rb-deficient embryos can be suppressed by deletion of E2f1, a known proliferation inducer that acts downstream of Rb. Thus, we conclude that pRb plays a key role in regulating osteoblast differentiation by mediating the inhibition of E2F and consequently promoting cell cycle exit.
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