The proto-oncogene function of Mdm2 in bone.
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.
['Olivos|David J|DJ|', 'Perrien|Daniel S|DS|', 'Hooker|Adam|A|', 'Cheng|Ying-Hua|YH|', 'Fuchs|Robyn K|RK|', 'Hong|Jung Min|JM|', 'Bruzzaniti|Angela|A|', 'Chun|Kristin|K|', 'Eischen|Christine M|CM|', 'Kacena|Melissa A|MA|', 'Mayo|Lindsey D|LD|0000-0002-5997-5166']
D000704:Analysis of Variance D000818:Animals D015519:Bone Density D016723:Bone Remodeling D002113:Calcification, Physiologic D000071556:Cancellous Bone D045744:Cell Line, Tumor D005260:Female D006801:Humans D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008811:Mice, Inbred DBA D010006:Osteoblasts D010010:Osteoclasts D010012:Osteogenesis D012516:Osteosarcoma D000090063:Proto-Oncogene Mas D051736:Proto-Oncogene Proteins c-mdm2 D011519:Proto-Oncogenes
mouse double minute 2 (Mdm2) bone mass osteoblast (OB)