title: IL-1β inhibits human osteoblast migration.
abstract: Bone has a high capacity for self-renewal and repair. Prolonged local secretion of interleukin 1β (IL-1β), however, is known to be associated with severe bone loss and delayed fracture healing. Since induction of bone resorption by IL-1β may not sufficiently explain these pathologic processes, we investigated, in vitro, if and how IL-1β affects migration of multipotent mesenchymal stromal cells (MSC) or osteoblasts. We found that homogenous exposure to IL-1β significantly diminished both nondirectional migration and site-directed migration toward the chemotactic factors platelet-derived growth factor (PDGF)-BB and insulin like growth factor 1 (IGF-1) in osteoblasts. Exposure to a concentration gradient of IL-1β induced an even stronger inhibition of migration and completely abolished the migratory response of osteoblasts toward PDGF-BB, IGF-1, vascular endothelial growth factor A (VEGF-A) and the complement factor C5a. IL-1β induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases (JNK) activation and inhibition of these signaling pathways suggested an involvement in the IL-1β effects on osteoblast migration. In contrast, basal migration of MSC and their migratory activity toward PDGF-BB was found to be unaffected by IL-1β. These results indicate that the presence of IL-1β leads to impaired recruitment of osteoblasts which might influence early stages of fracture healing and could have pathological relevance for bone remodeling in inflammatory bone disease.
authors.affiliation: Orthopedic Department, Division for Biochemistry of Joint and Connective Tissue Diseases, University of Ulm, Germany.
authors.forename: Nina-Emily
authors.initials: NE
authors.lastname: Hengartner
authors.forename: Jörg
authors.initials: J
authors.lastname: Fiedler
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Brenner
mesh_terms: D000077214:Becaplermin; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: C508590:IL1R1 protein, human; D053583:Interleukin-1beta; D020574:Proto-Oncogene Proteins c-sis; D053573:Receptors, Interleukin-1 Type I; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases