title: Human interleukin-1-induced murine osteoclastogenesis is dependent on RANKL, but independent of TNF-alpha.
abstract: Although interleukin-1 (IL-1) has been implicated in the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are largely unknown. Recently, a cytokine-driven, stromal cell-free mouse osteoclastogenesis model was established. A combination of macrophage colony stimulating factor (M-CSF) and receptor activator of NFkappaB ligand (RANKL) was proven to be sufficient in inducing differentiation of bone marrow hematopoietic precursor cells to bone-resorbing osteoclasts in the absence of stromal cells or osteoblasts. This study utilizes this model to examine the impact of human IL-1beta on in vitro osteoclastogenesis of bone marrow progenitor cells. We found that osteoclast precursor cells failed to undergo osteoclastogenesis when treated with IL-1 alone. In contrast, IL-1 dramatically up-regulated osteoclastogenesis by 2.5- to 4-folds in the presence of RANKL and M-CSF. The effect can be significantly blocked by IL-1 receptor antagonist (p < 0.01). Tumor necrosis factor-alpha (TNF-alpha) was undetectable in the culture medium of differentiating osteoclasts induced by IL-1. Adding exogenous TNF-alpha neutralizing antibody had no influence on the IL-1-induced effect as well. These results show that in the absence of stromal cells, IL-1 exacerbates osteoclastogenesis by cooperating with RANKL and M-CSF, while TNF-alpha is not involved in this IL-1-stimulated osteoclast differentiation pathway.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Edwards Building, R144, Stanford, CA 94305-5341, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Keita
authors.initials: K
authors.lastname: Miyanishi
authors.forename: Andrew
authors.initials: A
authors.lastname: Suen
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Epstein
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tomita
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha