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

Damien Eeles, Jason M Hodge, Preetinder Singh, Johannes A Schuijers, Brian L Grills, Matthew Todd Gillespie, Damian Eric Myers, Julian Michael Warner Quinn

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12 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)259 - 266
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume399
DOIs
Publication statusPublished - 2015

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