Osteoimmunology is the emerging concept that certain molecules
link the skeletal and immune
systems. The transcription factor c-Fos, a component of activator protein-1
(AP-1), is essential for
osteoclast differentiation. Mice lacking c-Fos are osteopetrotic owing
to impaired osteoclast development.
Recent studies suggest that in contrast to this positive role in osteoclastogenesis,
c-Fos expression
inhibits differentiation and activation of mononuclear phagocytes. Here,
we focus on the contrasting
roles of c-Fos in the bone and immune lineages. Both osteoclasts and mononuclear
phagocytes
are derived from common myeloid precursors. Osteoclasts resorb bone, whereas
macrophages and
myeloid dendritic cells phagocytose microbial pathogens, initiating innate
and adaptive immunity.
Differentiation of the common precursors into either bone or immune lineage
is determined by ligand
binding to cell-surface receptors, particularly receptor activator of NF-kB
(RANK) for osteoclasts, or
Toll-like receptors (TLRs) for mononuclear phagocytes. Both RANK and TLRs
activate the dimeric
transcription factors NF-kB and AP-1. Yet, c-Fos/AP-1 plays a positive
role in osteoclasts but a negative
role in macrophages and dendritic cells. Further study is necessary to
clarify this dual role of c-Fos.
(Keio J Med 53 (2): 78?84, June 2004) |