Cytokine-activated endothelium recruits osteoclast precursors.
Osteoclast precursors reach sites of osteoclast formation and remodelling via the vasculature and are therefore destined to encounter endothelium before migrating to the bone surface. Here we investigated the hypothesis that endothelium may be involved in the regulation of osteoclast precursor recruitment to sites of bone resorption. Osteoclast precursors in human peripheral blood were identified by their ability to form mature osteoclasts in 21-day cultures supplemented with RANKLigand, M-CSF, 1,25(OH)(2)-vitamin D(3), dexamethasone and prostaglandin E(2). Under control conditions few osteoclast precursors adhered to endothelial cells (the human bone marrow-derived endothelial cell line BMEC-1). However, BMEC-1 cells treated with the resorption stimulating cytokines IL-1beta and TNFalpha depleted the PBMC population of all osteoclast precursors. These results provide the first evidence that osteoclast precursors can adhere to endothelium and suggest that endothelium could play an important role in the recruitment of osteoclast precursors to sites of bone resorption.
Department of Medicine and Therapeutics, University of Aberdeen Medical School, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
N W
NW
McGowan
E J
EJ
Walker
H
H
Macpherson
S H
SH
Ralston
M H
MH
Helfrich
D001854:Bone Marrow Cells / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D002196:Capillaries / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D009000:Monocytes / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects
D016207:Cytokines