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.