The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Osteoblast differentiation and skeletal development are regulated by Mdm2–p53 signaling
Open accessAbstract
Mdm2 is required to negatively regulate p53 activity at the peri-implantation stage of early mouse development. However, the absolute requirement for Mdm2 throughout embryogenesis and in organogenesis is unknown. To explore Mdm2–p53 signaling in osteogenesis, Mdm2-conditional mice were bred with Col3.6-Cre–transgenic mice that express Cre recombinase in osteoblast lineage cells. Mdm2-conditional Col3.6-Cre mice die at birth and display multiple skeletal defects. Osteoblast progenitor cells deleted for Mdm2 have elevated p53 activity, reduced proliferation, reduced levels of the master osteoblast transcriptional regulator Runx2, and reduced differentiation. In contrast, p53-null osteoprogenitor cells have increased proliferation, increased expression of Runx2, increased osteoblast maturation, and increased tumorigenic potential, as mice specifically deleted for p53 in osteoblasts develop osteosarcomas. These results demonstrate that p53 plays a critical role in bone organogenesis and homeostasis by negatively regulating bone development and growth and by suppressing bone neoplasia and that Mdm2-mediated inhibition of p53 function is a prerequisite for Runx2 activation, osteoblast differentiation, and proper skeletal formation.
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“In contrast to these scenarios, p53 can also suppress differentiation, as exemplified by its ability to inhibit osteoblast differentiation and bone development in mice (Lengner et al., 2006; Wang et al., 2006).”
From p53 at a glance (2010) · cites this paper as Lengner et al., 2006
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Cites
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 1×
“In addition, Mdm2 can function as an E3 ligase to coordinate the ubiquitination of p53 (Honda et al., 1997) and can induce the degradation of p53 by the 26S proteasome (Haupt et al., 1997; Kubbutat et al., 1997; Li et al., 2003).”
BackgroundSelf-citationMomand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113
Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
Honda, R., Tanaka, H., & Yasuda, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01480-4 · Cited by 1,951
p53 mutant mice that display early ageing-associated phenotypes
Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., et al. (2002) · Nature · doi:10.1038/415045a · Cited by 1,459 · cited 3×
“In contrast, a recently generated mouse model bearing a mutated p53 allele (m allele) that increased p53 activity in vitro displayed early aging-like phenotypes, including reduced mass of various internal organs, thinning of the dermis, hair loss, and osteoporosis (Tyner et al., 2002).”
BackgroundInfluentialSelf-citationRescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
de Oca Luna, R. M., Wagner, D. S., & Lozano, G. (1995) · Nature · doi:10.1038/378203a0 · Cited by 1,420 · cited 3×
“…lethality by deletion of p53 demonstrates that Mdm2 plays an important role in early development by negatively regulating p53 activity (Jones et al., 1995; Montes de Oca Luna et al., 1995), on A ugust 18, 2017 jcb.rupress.org D ow nloaded from MDM2–P53 REGULATION OF OSTEOGENESIS • LENGNER ET AL.”
BackgroundRescue of embryonic lethality in Mdm2-deficient mice by absence of p53
Jones, S. N., Roe, A. E., Donehower, L. A., & Bradley, A. (1995) · Nature · doi:10.1038/378206a0 · Cited by 1,280
Self-citation
Cited by
Brady, C. A., & Attardi, L. D. (2010) · Journal of Cell Science · doi:10.1242/jcs.064501 · Cited by 403
The RUNX family: developmental regulators in cancer
Ito, Y., Bae, S.-C., & Chuang, L. S. H. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3877 · Cited by 399
DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age
Kim, H., Chang, J., Shao, L., Han, L., Iyer, S., Manolagas, S. C., O'Brien, C. A., Jilka, R. L., Zhou, D., & Almeida, M. (2017) · Aging Cell · doi:10.1111/acel.12597 · Cited by 192
Cell Death in Chondrocytes, Osteoblasts, and Osteocytes
Komori, T. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122045 · Cited by 176
“6-kb Col1a1 promoter in Cre transgenic mice resulted in reduced bone formation, and the differentiation of primary osteoblasts was inhibited in vitro [87].”
BackgroundOsteosarcoma: Molecular Pathogenesis and iPSC Modeling
Lin, Y.-H., Jewell, B. E., Gingold, J., Lu, L., Zhao, R., Wang, L. L., & Lee, D.-F. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.06.004 · Cited by 150
Metadata
- Authors
- Lengner, C. J., Steinman, H. A., Gagnon, J., Smith, T. W., Henderson, J. E., Kream, B. E., Stein, G. S., Lian, J. B., & Jones, S. N.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2006-03-13
- Volume
- 172
- Issue
- 6
- Pages
- 909-921
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2003946870
- Cited by
- 265
- References
- 12
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- green
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- Lengner, C. J., Steinman, H. A., Gagnon, J., Smith, T. W., Henderson, J. E., Kream, B. E., Stein, G. S., Lian, J. B., & Jones, S. N. (2006). Osteoblast differentiation and skeletal development are regulated by Mdm2–p53 signaling. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200508130
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
