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Osteoclast formation elicited by interleukin-33 stimulation is dependent upon the type of osteoclast progenitor


Osteoclasts are bone resorbing multinucleated cells (MNCs) derived from macrophage progenitors. IL-33 has been reported to drive osteoclastogenesis independently of receptor activator of NFkappaB ligand (RANKL) but this remains controversial as later studies did not confirm this. We found IL-33 clearly elicited functional dentine-resorbing osteoclast formation from human adult monocytes. However, monocytes from only 3 of 12 donors responded this way, while all responded to RANKL. Human cord blood-derived progenitors and murine bone marrow macrophages lacked an osteoclastogenic response to IL-33. In RAW264.7 cells, IL-33 elicited NFkappaB and p38 responses but not NFATc1 signals (suggesting poor osteoclastogenic responses) and formed only mononuclear tartrate-resistant acid phosphatase positive (TRAP(+)) cells. Since TGFbeta boosts osteoclastogenesis in RAW264.7 cells we employed an IL-33/TGFbeta co-treatment, which resulted in small numbers of MNCs expressing key osteoclast markers TRAP and calcitonin receptors. Thus, IL-33 possesses weak osteoclastogenic activity suggesting pathological significance and, perhaps, explaining previous conflicting reports.

Type Journal
ISBN 1872-8057 (Electronic) 0303-7207 (Linking)
Authors Eeles, D. G. ; Hodge, J. M. ; Singh, P. P. ; Schuijers, J. A. ; Grills, B. L. ; Gillespie, M. T. ; Myers, D. E. ; Quinn, J. M.;
Responsible Garvan Author Dr Julian Quinn
Published Date 2015-01-01
Published Volume 399
Published Pages 259-66
Status Published in-print
URL link to publisher's version