First Author | Olivos DJ 3rd | Year | 2018 |
Journal | J Cell Biochem | Volume | 119 |
Issue | 11 | Pages | 8830-8840 |
PubMed ID | 30011084 | Mgi Jnum | J:289592 |
Mgi Id | MGI:6434632 | Doi | 10.1002/jcb.27133 |
Citation | Olivos DJ 3rd, et al. (2018) The proto-oncogene function of Mdm2 in bone. J Cell Biochem 119(11):8830-8840 |
abstractText | 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(Tg) ) 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(TgOb) ) 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. |