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The proto-oncogene function of Mdm2 in bone.

David J Olivos1,2,3, Daniel S Perrien4,5, Adam Hooker2

  • 1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.

Journal of Cellular Biochemistry
|July 17, 2018
PubMed
Summary

Mouse double minute 2 (Mdm2) overexpression in specific cells promotes bone health. This proto-oncogene

Keywords:
bone massmouse double minute 2 (Mdm2)osteoblast (OB)

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Area of Science:

  • Oncology
  • Bone Biology
  • Genetics

Background:

  • Mouse double minute 2 (Mdm2) is a key oncoprotein with critical roles in cellular transformation.
  • Mdm2's embryonic lethality necessitates genetic modifications for in vivo study.
  • Global Mdm2 overexpression (Mdm2Tg) leads to hematopoietic neoplasms and sarcomas.

Purpose of the Study:

  • To investigate the role of Mdm2 in bone biology, specifically osteoblastogenesis and bone mass.
  • To determine if Mdm2 overexpression in osteoblasts causes malignancies.
  • To assess Mdm2's potential in reversing age-related bone loss.

Main Methods:

  • Generation of global Mdm2 transgenic mice (Mdm2Tg).
  • Creation of osteoblast-specific Mdm2 transgenic mice (Mdm2TgOb) in C57BL/6 and DBA strains.
  • Analysis of bone mineralization, osteoblastogenesis, and tumor development in transgenic mice and MG63 cells.

Main Results:

  • Global Mdm2 overexpression resulted in increased osteoblastogenesis, differentiation, and high bone mass.
  • Osteoblast-specific Mdm2 overexpression did not induce malignancies but increased bone mineralization.
  • Mdm2 overexpression ameliorated age-related bone loss in mice.

Conclusions:

  • Mdm2 plays a significant role in regulating bone mass and mineralization.
  • Targeted Mdm2 overexpression in osteoblasts enhances bone health without causing cancer.
  • Mdm2's proto-oncogenic activity is linked to maintaining bone health in adult animals.