title: IL-1alpha and IL-1beta have different effects on formation and activity of large osteoclasts.
abstract: Interleukin 1 (IL-1) is a proinflammatory cytokine upregulated in conditions such as rheumatoid arthritis and periodontal disease. Both isoforms, IL-1alpha and IL-1beta, have been shown to activate osteoclasts (OCs), the cells responsible for resorbing bone. Inflammatory conditions are also characterized by increased bone loss and by the presence of large OCs (10+ nuclei). We and others have previously shown that large OCs are more likely to be resorbing compared to small OCs (2-5 nuclei). Moreover, large OCs express higher levels of the IL-1 activating receptor IL-1RI, integrins alphav and beta3, RANK, and TNFR1, while small OCs have higher levels of the decoy receptor IL-1RII. We hypothesized that IL-1 would have different effects on large and small OCs due to these distinct receptor expression patterns. To test this hypothesis, RAW 264.7 cells were differentiated into populations of small and large OCs and treated with IL-1alpha or IL-1beta (1 and 10 ng/ml). In the presence of sRANKL, both IL-1alpha and IL-1beta increased total OC number and resorptive activity of large OCs. IL-1alpha stimulated formation of large OCs and increased the number of resorption pits, while IL-1beta changed the morphology of large OCs and integrin-beta3 phosphorylation. No effects were seen in small OCs in response to either IL-1 isoform. These results demonstrate that IL-1 predominantly affects large OCs. The dissimilarity of responses to IL-1alpha and IL-1beta suggests that these isoforms activate different signaling pathways within the two OC populations.
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, ON, Canada. diana.trebec@utoronto.ca
authors.forename: Diana P
authors.initials: DP
authors.lastname: Trebec-Reynolds
authors.forename: Irina
authors.initials: I
authors.lastname: Voronov
authors.forename: Johan N M
authors.initials: JN
authors.lastname: Heersche
authors.forename: Morris F
authors.initials: MF
authors.lastname: Manolson
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D039661:Integrin beta3 / Q000378:metabolism; D053582:Interleukin-1alpha / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017472:Receptors, Interleukin-1 / Q000378:metabolism
chemical_list: D039661:Integrin beta3; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1