title: IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling.
abstract: The aim of the present study was to investigate the potential role of the recently discovered IL-1 family member IL-33 in bone remodeling. Our results indicate that IL-33 mRNA is expressed in osteocytes in non-inflammatory human bone. Moreover, IL-33 levels are increased by TNF-α and IL-1β in human bone marrow stromal cells, osteoblasts and adipocytes obtained from three healthy donors. Experiments with the inhibitor GW-9662 suggested that expression of IL-33, in contrast to that of IL-1β, is not repressed by PPARγ likely explaining why IL-33, but not IL-1β, is expressed in adipocytes. The IL-33 receptor ST2L is not constitutively expressed in human bone marrow stromal cells, osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells. In addition, although ST2L mRNA is induced by TNF-α and IL-1β in bone marrow stromal cells, IL-33 has the same effects as TNF-α and IL-1β, and, therefore, the biological activity of IL-33 may be redundant in this system. In agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively express ST2L mRNA, and IL-33 and TNF-α/IL-1β similarly decrease osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL-33 has no direct effects on normal bone remodeling.
authors.affiliation: Physiopathology of Inflammatory Bone Diseases, EA2603, University Lille North of France, Quai Masset, Bassin Napoléon BP120, 62327 Boulogne/Mer, France. saidisoraya@yahoo.fr
authors.forename: S
authors.initials: S
authors.lastname: Saidi
authors.forename: F
authors.initials: F
authors.lastname: Bouri
authors.forename: P
authors.initials: P
authors.lastname: Lencel
authors.forename: L
authors.initials: L
authors.lastname: Duplomb
authors.forename: M
authors.initials: M
authors.lastname: Baud'huin
authors.forename: S
authors.initials: S
authors.lastname: Delplace
authors.forename: D
authors.initials: D
authors.lastname: Leterme
authors.forename: F
authors.initials: F
authors.lastname: Miellot
authors.forename: D
authors.initials: D
authors.lastname: Heymann
authors.forename: P
authors.initials: P
authors.lastname: Hardouin
authors.forename: G
authors.initials: G
authors.lastname: Palmer
authors.forename: D
authors.initials: D
authors.lastname: Magne
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D016723:Bone Remodeling; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta / Q000494:pharmacology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; C530318:ST2L protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin