Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappa B (RANK) receptors
F. Arai et al., Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappa B (RANK) receptors, J EXP MED, 190(12), 1999, pp. 1741-1754
Osteoclasts are terminally differentiated cells derived from hematopoietic
stem cells. However, how their precursor cells diverge from macrophagic lin
eages is not known. We have identified early and late stages of osteoclasto
genesis, in which precursor cells sequentially express c-Fms followed by re
ceptor activator of nuclear factor kappa B (RANK), and have demonstrated th
at RANK expression in early-stage of precursor cells (c-Fms(+)RANK(-)) was
stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF
and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms(
+)RANK(+)) into osteoclasts, even late-stage precursors have the potential
to differentiate into macrophages without RANKL. Pretreatment of precursors
with M-CSF and delayed addition of RANKL showed that timing of RANK expres
sion and subsequent binding of RANKL are critical for osteoclastogenesis. T
hus, the RANK-RANKL system determines the osteoclast differentiation of bip
otential precursors in the default pathway of macrophage differentiation.