Fra-1 potentiates osteoclastic differentiation in osteoclast-macrophage precursor cell lines

J Cell Physiol. 1999 May;179(2):170-8. doi: 10.1002/(SICI)1097-4652(199905)179:2<170::AID-JCP7>3.0.CO;2-K.


c-Fos, a component of the dimeric transcription factor AP-1, is necessary for osteoclast formation. To determine whether c-Fos can substitute for any or all of the stimuli needed for osteoclast induction, we infected osteoclast precursors with retroviral vectors expressing c-Fos or the Fos-related protein, Fra-1. The infected cells were incubated with or without osteoclast-inductive stimuli. Osteoclast formation from retroviral-infected precursors remained completely dependent on osteoclast-inductive stromal cells. Unexpectedly, infection of bipotential osteoclast-macrophage precursor cell lines with retroviruses expressing Fra-1 but not c-Fos caused a 10-100-fold increase in the number of precursors that developed calcitonin receptors associated with an increase in bone resorption. These observations suggest that, in the precursor cell lines, Fra-1 is a limiting factor for full responsiveness to the osteoclast-inductive environment. Fra-1 is therefore likely to play a role in osteoclast differentiation which is distinct from that of c-Fos.

MeSH terms

  • Autoradiography
  • Bone Resorption / metabolism
  • Cell Differentiation / genetics*
  • Cell Line
  • Gene Expression Regulation / genetics
  • Macrophage Colony-Stimulating Factor / metabolism
  • Macrophages / metabolism*
  • Osteoclasts / metabolism*
  • Phenotype
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / analysis
  • Receptors, Calcitonin / metabolism
  • Retroviridae / genetics
  • Transfection / genetics


  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Calcitonin
  • fos-related antigen 1
  • Macrophage Colony-Stimulating Factor