Fra-1 potentiates osteoclastic differentiation in osteoclast-macrophage precursor cell lines.
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.
Owens
J M
JM
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
Matsuo
K
K
Nicholson
G C
GC
Wagner
E F
EF
Chambers
T J
TJ
D001345:Autoradiography; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018003:Receptors, Calcitonin / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014162:Transfection / Q000235:genetics; D000099169:Fos-Related Antigen 1
D016173:Macrophage Colony-Stimulating Factor; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D000099169:Fos-Related Antigen 1