Death receptors, Fas and TRAIL receptors, are involved in human osteoclast apoptosis.
Survival and apoptosis are crucial aspects of the osteoclast life cycle. Although osteoclast survival has been extensively studied, little is known about the mechanisms involved in human osteoclast apoptosis. In the present study, cord blood monocytes (CBMs) were used as the source of human osteoclast precursors. When cultured in the presence of M-CSF and RANKL, CBMs formed multinucleated cells that expressed RANK and calcitonin receptor, and were able to resorb bone. These cells expressed TRAIL receptors (R1-R4). Surprisingly, although TRAIL-receptor expression was not detectable in osteoclasts from normal bone, osteoclasts from myeloma specimens did express TRAIL receptors to a variable extent. Significantly, we have shown for the first time that this pathway is indeed functional in human osteoclasts, and that apoptosis occurred and was significantly greater in the presence of TRAIL. In addition, we have shown that a Fas-activating antibody is also able to induce osteoclast apoptosis, as did TGFbeta, whereas the survival factor M-CSF decreased apoptosis. Overall, these findings suggest that death receptors, TRAIL receptors and Fas, could be involved in osteoclast apoptosis in humans.
Roux
Sophie
S
Department of Medicine, Division of Rheumatology, Sherbrooke University, Quebec, Canada. sophie.roux@usherbrooke.ca
Lambert-Comeau
Pascal
P
Saint-Pierre
Céline
C
Lépine
Mariette
M
Sawan
Bassem
B
Parent
Jean-Luc
JL
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor