IL-1β Inhibits Human Osteoblast Migration

Bone has a high capacity for self-renewal and repair. Prolonged local secretion of interleukin 1 beta (IL-1 beta), however, is known to be associated with severe bone loss and delayed fracture healing. Since induction of bone resorption by IL-1 beta may not sufficiently explain these pathologic processes, we investigated, in vitro, if and how IL-1 beta affects migration of multipotent mesenchymal stromal cells (MSC) or osteoblasts. We found that homogenous exposure to IL-1 beta significantly diminished both nondirectional migration and site-directed migration toward the chemotactic factors platelet-derived growth factor (PDGF)-BB and insulinlike growth factor 1 (IGF-1) in osteoblasts. Exposure to a concentration gradient of IL-1 beta 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-1 beta 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-1 beta effects on osteoblast migration. In contrast, basal migration of MSC and their migratory activity toward PDGF-BB was found to be unaffected by IL-1 beta. These results indicate that the presence of IL-1 beta 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.