title: Osteoclast formation elicited by interleukin-33 stimulation is dependent upon the type of osteoclast progenitor.
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.
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia; Department of Human Biosciences, La Trobe University, Bundoora, VIC, Australia.
authors.forename: Damien G
authors.initials: DG
authors.lastname: Eeles
authors.affiliation: Barwon Biomedical Research, Department of Medicine, The Geelong Hospital, Geelong, VIC, Australia; School of Medicine, Deakin University, Geelong, VIC, Australia.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hodge
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia.
authors.forename: Preetinder P
authors.initials: PP
authors.lastname: Singh
authors.affiliation: Department of Human Biosciences, La Trobe University, Bundoora, VIC, Australia.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Schuijers
authors.affiliation: Department of Human Biosciences, La Trobe University, Bundoora, VIC, Australia.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Grills
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Gillespie
authors.affiliation: Department of Orthopaedics, St Vincent's Hospital, Fitzroy, VIC, Australia; Department of Surgery, St Vincent's Hospital, Fitzroy, VIC, Australia.
authors.forename: Damian E
authors.initials: DE
authors.lastname: Myers
authors.affiliation: 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.
authors.forename: Julian M W
authors.initials: JM
authors.lastname: Quinn
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C506536:IL33 protein, human; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Bone resorption; Interleukin; Osteoclast; Th2 cytokine