Rapamycin and the transcription factor C/EBPbeta as a switch in osteoclast differentiation: implications for lytic bone diseases.
Lytic bone diseases and in particular osteoporosis are common age-related diseases characterized by enhanced bone fragility due to loss of bone density. Increasingly, osteoporosis poses a major global health-care problem due to the growth of the elderly population. Recently, it was found that the gene regulatory transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) is involved in bone metabolism. C/EBPbeta occurs as different protein isoforms of variable amino terminal length, and regulation of the C/EBPbeta isoform ratio balance was found to represent an important factor in osteoclast differentiation and bone homeostasis. Interestingly, adjustment of the C/EBPbeta isoform ratio by the process of translational control is downstream of the mammalian target of rapamycin kinase (mTOR), a sensor of the nutritional status and a target of immunosuppressive and anticancer drugs. The findings imply that modulating the process of translational control of C/EBPbeta isoform expression could represent a novel therapeutic approach in osteolytic bone diseases, including cancer and infection-induced bone loss.
Smink
Jeske J
JJ
Max Delbrueck Center for Molecular Medicine, Humboldt University Berlin, Institute of Biology, Berlin-Brandenburg Center for Regenerative Therapies, Robert-Roessle-Strasse 10, Berlin, Germany.
Leutz
Achim
A
D000818:Animals; D001847:Bone Diseases / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*
D022782:CCAAT-Enhancer-Binding Protein-beta; D020123:Sirolimus