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The proto‐oncogene function of Mdm2 in bone
Author(s) -
Olivos David J.,
Perrien Daniel S.,
Hooker Adam,
Cheng YingHua,
Fuchs Robyn K.,
Hong Jung Min,
Bruzzaniti Angela,
Chun Kristin,
Eischen Christine M.,
Kacena Melissa A.,
Mayo Lindsey D.
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27133
Subject(s) - mdm2 , phenotype , oncogene , biology , cancer research , osteosarcoma , osteoblast , gene , microbiology and biotechnology , lineage (genetic) , haematopoiesis , genetics , in vitro , stem cell , cell cycle
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.