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

Abstract

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.

• Authors: J M Owens, K Matsuo, G C Nicholson, E F Wagner, T J Chambers
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 179 Issue 2 Pg. 170-8 (May 1999) ISSN: 0021-9541 [Print] United States
• PMID: 10199556 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, metabolism)
• RNA, Messenger (analysis)
• Receptors, Calcitonin (metabolism)
• Retroviridae (genetics)
• Transfection (genetics)