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Mol Cell Endocrinol. 2015 Jan 5;399:259-66. doi: 10.1016/j.mce.2014.10.014. Epub 2014 Oct 18.

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

Author information

1
MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia; Department of Human Biosciences, La Trobe University, Bundoora, VIC, Australia.
2
Barwon Biomedical Research, Department of Medicine, The Geelong Hospital, Geelong, VIC, Australia; School of Medicine, Deakin University, Geelong, VIC, Australia.
3
MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia.
4
Department of Human Biosciences, La Trobe University, Bundoora, VIC, Australia.
5
MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
6
Department of Orthopaedics, St Vincent's Hospital, Fitzroy, VIC, Australia; Department of Surgery, St Vincent's Hospital, Fitzroy, VIC, Australia.
7
MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia. Electronic address: j.quinn@garvan.org.au.

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 NFκB 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 NFκB and p38 responses but not NFATc1 signals (suggesting poor osteoclastogenic responses) and formed only mononuclear tartrate-resistant acid phosphatase positive (TRAP(+)) cells. Since TGFβ boosts osteoclastogenesis in RAW264.7 cells we employed an IL-33/TGFβ 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.

KEYWORDS:

Bone resorption; Interleukin; Osteoclast; Th2 cytokine

PMID:
25458701
DOI:
10.1016/j.mce.2014.10.014
[Indexed for MEDLINE]

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