title: Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro.
abstract: TRAIL (TNF-related apoptosis-inducing ligand) has been shown to induce apoptosis by binding to TRAIL-R1 and -R2 death receptors, but not to TRAIL-R3 or -R4, its decoy receptors that lack the internal death domain. Osteoclasts (Ocs) are sensitive to TRAIL-induced apoptosis, and modulation of these receptors may change Oc sensitivity to TRAIL. Using human Oc cultures, we first investigated the gene expression profile of these receptors (TNFRSF10 -A, -B, -C, -D encoding TRAIL-Rs 1-4) by real time PCR after adding osteotropic factors during the last week of Oc cultures. We observed a significant decrease in the expression of TNFRSF10-A after the addition of TGFβ, and an increase in that of TNFRSF10-A and -B post-PTH stimulation. Protein expression of TRAIL-R1 and -R3 was upregulated in the presence of MIP-1α, but down-regulated in the presence of TGFβ (R1), TRAIL (R2) or OPG (R3). The percentage of Ocs expressing the TRAIL-R1 and/or -R2 at their surface was increased by MIP-1α and TRAIL, increased (R2) or decreased (R1) by TGFβ, and the percentage expressing TRAIL-R3 was increased by MIP-1α, TRAIL and RANKL. Although significant, the magnitude of all these changes was of about 10-15%. While a direct correlation between these changes and TRAIL-induced Oc apoptosis was less clear, a protective effect was observed in Ocs that had been treated with OPG, and an additive effect in Ocs pre-treated with TRAIL or TGFβ increased TRAIL sensitivity.
authors.affiliation: Division of Rheumatology, Faculty of Medicine, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, PQ, J1H5N4, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: McManus
authors.forename: Estelle
authors.initials: E
authors.lastname: Chamoux
authors.forename: Martine
authors.initials: M
authors.lastname: Bisson
authors.forename: Sophie
authors.initials: S
authors.lastname: Roux
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001862:Bone Resorption / Q000378:metabolism*; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000166:cytology; D010010:Osteoclasts / Q000378:metabolism*; D011247:Pregnancy; D053245:RANK Ligand / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D054405:Chemokine CCL3; D053245:RANK Ligand; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505688:TNFSF11 protein, human; D016212:Transforming Growth Factor beta