title: Transgenic over-expression of interleukin-33 in osteoblasts results in decreased osteoclastogenesis.
abstract: Interleukin-33 (IL-33) is the most recently identified member of the IL-1 family of cytokines, which is primarily known for its proinflammatory functions. We have previously reported that IL-33 is expressed by bone-forming osteoblasts, and that administration of recombinant IL-33 to bone marrow cultures inhibits their differentiation into bone-resorbing osteoclasts. Likewise, while the inhibitory effect of IL-33 on osteoclast differentiation was fully abolished in cultures lacking the IL-33 receptor ST2, mice lacking ST2 displayed low bone mass caused by increased osteoclastogenesis. Although these data suggested a physiological role of IL-33 as an inhibitor of bone resorption, direct in vivo evidence supporting such a function was still missing. Here we describe the generation and bone histomorphometric analysis of a transgenic mouse model (Col1a1-Il33) over-expressing IL-33 specifically in osteoblasts. While we did not observe differences in osteoblast number and bone formation between wildtype and Col1a1-Il33 mice, the number of osteoclasts was significantly reduced compared to wildtype littermates in two independent transgenic lines. Since we did not observe quantitative differences in the populations of eosinophils, neutrophils, basophils or M2-macrophages from the bone marrow of wildtype and Col1a1-Il33 mice, our data demonstrate that an inhibition of osteoclastogenesis is one of the major physiological functions of IL-33, at least in mice.
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Keller
authors.forename: Philip
authors.initials: P
authors.lastname: Catala-Lehnen
authors.forename: Kristofer
authors.initials: K
authors.lastname: Wintges
authors.forename: Jochen
authors.initials: J
authors.lastname: Schulze
authors.forename: Thomas
authors.initials: T
authors.lastname: Bickert
authors.forename: Wulf
authors.initials: W
authors.lastname: Ito
authors.forename: Andrea Kristina
authors.initials: AK
authors.lastname: Horst
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D019076:Transgenes
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins