Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappa B (RANK) receptors

Citation
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
Citations number
51
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF EXPERIMENTAL MEDICINE
ISSN journal
00221007 → ACNP
Volume
190
Issue
12
Year of publication
1999
Pages
1741 - 1754
Database
ISI
SICI code
0022-1007(199912)190:12<1741:CADOOP>2.0.ZU;2-V
Abstract
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.