LTB4 can directly stimulate human osteoclast formation from PBMC independent of RANKL.
Leukotriene B4, as a kind of 5-lipoxygenase metabolite of arachidonic acid, is known to influence osteoclast formation and bone resorption. In order to determine whether Leukotriene B4 could directly stimulate human osteoclast differentiation and activation independent of RANKL (ODF), three different concentrations of Leukotriene B4 (10(-9)M, 10(-8)M, 10(-7)M) were added to the culture of CD14+ monocyte fraction of peripheral blood mononuclear cell (PBMC) in the presence of macrophage colony-stimulating factor (M-CSF). Under these conditions, Leukotriene B4 could induce multinucleated cells, which were positive for Tartrate-resistant acidic phosphatase (TRAP) staining and capable of bone resorption. Addition of osteoprotegerin (OPG) to PBMC cultures does not abrogate osteoclast formation induced by LTB4. Osteoclastogenesis induced by Leukotriene B4 were dose-dependently increased and weaker than that of RANKL. These results indicated that Leukotriene B4, elevated in many inflammatory diseases, is directly capable of inducing osteoclast formation by a RANKL-independent mechanism.
Jiang
Jun
J
Arthritis Clinic & Research Center, Peking University People's Hospital, Beijing, China.
Lv
Hou-shan
HS
Lin
Jian-hao
JH
Jiang
Dong-fang
DF
Chen
Zhan-kun
ZK
D001862:Bone Resorption; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D007975:Leukotriene B4; D016173:Macrophage Colony-Stimulating Factor