Rapamycin and the transcription factor C/EBPbeta as a switch in osteoclast differentiation: implications for lytic bone diseases

J Mol Med (Berl). 2010 Mar;88(3):227-33. doi: 10.1007/s00109-009-0567-8. Epub 2009 Nov 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Diseases / metabolism*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Differentiation*
  • Humans
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • Sirolimus / pharmacology*

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Sirolimus