RRC ID 68526
Author Gorny G, Shaw A, Oursler MJ.
Title IL-6, LIF, and TNF-alpha regulation of GM-CSF inhibition of osteoclastogenesis in vitro.
Journal Exp Cell Res
Abstract During pathological bone loss, factors that are both stimulatory and inhibitory for osteoclast differentiation are over-expressed. Despite the presence of inhibitory factors, osteoclast differentiation is significantly enhanced to bring about bone loss. To examine the hypothesis that stimulatory growth factors overcome the effects of inhibitory factors, we have examined the ability of IGF-I, IGF-II, IL-6, LIF, and TNF-alpha to overcome osteoclast differentiation inhibition by GM-CSF in vitro. Osteoclast numbers were significantly elevated by treatment with IGF-I, IGF-II, IL-6, LIF, or TNF-alpha alone whereas GM-CSF treatment of stromal cell and osteoclast co-cultures inhibited osteoclast formation. IL-6, LIF, or TNF-alpha, individually overcame GM-CSF inhibition whereas neither IGF-I nor IGF-II treatment overcame GM-CSF inhibition. Interestingly, GM-CSF addition with either IL-6 or TNF-alpha increased osteoclast numbers beyond that seen with either IL-6 or TNF-alpha alone. Combined treatment with TNF-alpha and IL-6 showed a significant increase in osteoclast numbers with GM-CSF addition. Examination of the impacts of these growth factors individually or in combinations on stromal cell M-CSF, RANKL, and OPG expression revealed a complex pattern involving alterations in the ratio of RANKL to OPG and/or M-CSF expression as candidate mechanisms of action.
Volume 294(1)
Pages 149-58
Published 2004-3-10
DOI 10.1016/j.yexcr.2003.11.009
PII S0014482703005950
PMID 14980510
MeSH Animals Carrier Proteins / metabolism Cell Differentiation / drug effects Cells, Cultured Drug Synergism Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors* Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / drug effects Interleukin-6 / pharmacology* Leukemia Inhibitory Factor Male Membrane Glycoproteins / metabolism Mice Mice, Inbred BALB C Osteoclasts / cytology* Osteoclasts / drug effects Osteoclasts / metabolism RANK Ligand Receptor Activator of Nuclear Factor-kappa B Receptor, Macrophage Colony-Stimulating Factor / metabolism Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism Somatomedins / pharmacology Tumor Necrosis Factor-alpha / pharmacology*
IF 3.383
Human and Animal Cells ST2(RCB0224)