Interleukin-6 and interleukin-11 support human osteoclast formation by a RANKL-independent mechanism.
Interleukin-6 (IL-6) and interleukin-11 (IL-11) are known to influence osteoclast formation and bone resorption. In order to determine whether IL-6 and IL-11 could independently support human osteoclast formation, these factors were added to cultures of human peripheral blood mononuclear cells of the monocyte (CD14(+)) fraction in the presence of macrophage colony-stimulating factor (M-CSF). Under these conditions, IL-6 and IL-11 induced the formation of multinucleated cells which were positive for TRAP, VNR, and calcitonin receptor and capable of lacunar resorption. Osteoclastogenesis induced by IL-6 and IL-11 was inhibited by the addition of an anti-gp130 antibody but not by osteoprotegerin. These results indicate that IL-6 and IL-11, which are thought to play a role in several osteolytic bone disorders, are directly capable of inducing osteoclast formation by a RANKL-independent mechanism.
Kudo
O
O
Department of Pathology, Nuffield Department of Orthopaedic Surgery, University of Oxford, Windmill Road, Headington, Oxford OX3 7LD, UK.
Sabokbar
A
A
Pocock
A
A
Itonaga
I
I
Fujikawa
Y
Y
Athanasou
N A
NA
D000135:Acid Phosphatase / Q000096:biosynthesis; D000328:Adult; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011994:Recombinant Proteins / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase
D002352:Carrier Proteins; D017370:Interleukin-11; D015850:Interleukin-6; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011994:Recombinant Proteins; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase