The proto-oncogene function of Mdm2 in bone

David J. Olivos, Daniel S. Perrien, Adam Hooker, Ying Hua Cheng, Robyn K. Fuchs, Jung Min Hong, Angela Bruzzaniti, Kristin Chun, Christine M. Eischen, Melissa A. Kacena, Lindsey D. Mayo

Research output: Contribution to journalArticle

Abstract

Mouse double minute 2 (Mdm2) is a multifaceted oncoprotein that is highly regulated with distinct domains capable of cellular transformation. Loss of Mdm2 is embryonically lethal, making it difficult to study in a mouse model without additional genetic alterations. Global overexpression through increased Mdm2 gene copy number (Mdm2Tg) results in the development of hematopoietic neoplasms and sarcomas in adult animals. In these mice, we found an increase in osteoblastogenesis, differentiation, and a high bone mass phenotype. Since it was difficult to discern the cell lineage that generated this phenotype, we generated osteoblast-specific Mdm2 overexpressing (Mdm2TgOb) mice in 2 different strains, C57BL/6 and DBA. These mice did not develop malignancies; however, these animals and the MG63 human osteosarcoma cell line with high levels of Mdm2 showed an increase in bone mineralization. Importantly, overexpression of Mdm2 corrected age-related bone loss in mice, providing a role for the proto-oncogenic activity of Mdm2 in bone health of adult animals.

Original languageEnglish (US)
Pages (from-to)8830-8840
Number of pages11
JournalJournal of Cellular Biochemistry
Volume119
Issue number11
DOIs
StatePublished - Nov 2018

Keywords

  • bone mass
  • mouse double minute 2 (Mdm2)
  • osteoblast (OB)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Olivos, D. J., Perrien, D. S., Hooker, A., Cheng, Y. H., Fuchs, R. K., Hong, J. M., Bruzzaniti, A., Chun, K., Eischen, C. M., Kacena, M. A., & Mayo, L. D. (2018). The proto-oncogene function of Mdm2 in bone. Journal of Cellular Biochemistry, 119(11), 8830-8840. https://doi.org/10.1002/jcb.27133