The proto-oncogene function of Mdm2 in bone.

Olivos DJ, Perrien DS, Hooker A, Cheng YH, Fuchs RK, Hong JM, Bruzzaniti A, Chun K, Eischen CM, Kacena MA, Mayo LD
J Cell Biochem. 2018 119 (11): 8830-8840

PMID: 30011084 · PMCID: PMC6348883 · DOI:10.1002/jcb.27133

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 (Mdm2 ) 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 (Mdm2 ) 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.

© 2018 Wiley Periodicals, Inc.

MeSH Terms (19)

Analysis of Variance Animals Bone Density Bone Remodeling Calcification, Physiologic Cancellous Bone Cell Line, Tumor Female Humans Male Mice Mice, Inbred C57BL Mice, Inbred DBA Osteoblasts Osteoclasts Osteogenesis Osteosarcoma Proto-Oncogene Proteins c-mdm2 Proto-Oncogenes

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