title: Temporal differential effects of proinflammatory cytokines on osteoclastogenesis.
abstract: Bone destruction and inflammation are closely linked. Cytokines play an important role in inflammatory bone destruction by upregulating the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). The direct role of cytokines that act in a non-RANKL-dependent manner has yet to be elucidated. The aim of this study was to investigate the direct osteoclastogenic properties of inflammatory cytokines at different time-points of osteoclastogenesis. Mouse bone marrow macrophages were stimulated with the macrophage colony-stimulating factor (M-CSF) and various concentrations of RANKL. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17 and IL-23, were added to the culture system of osteoclastogenesis. Two time-points of cytokine treatment were set. The 'early' effect of each cytokine was investigated at the time of first RANKL treatment, whereas the 'late' effect was investigated 48 h after the first RANKL challenge. Osteoclast differentiation and function were assessed using an osteoclast marker [tartrate-resistant acid phosphatase (TRAP)] and by visualization of pit formation. A permissive level of RANKL was required for cytokine-associated osteoclastogenesis in all experiments. In the M-CSF/RANKL monocellular culture system, IL-1β enhanced and IL-6 decreased osteoclast formation in a dose-dependent manner, regardless of temporal differences. Other cytokines showed various responses according to the phase of osteoclast maturation and the concentration of each cytokine and RANKL. Furthermore, luciferase assays showed that both IL-1β and RANKL activated the NF-κB signaling pathway. Collectively, our data revealed that targeting IL-1β may be a promising strategy to inhibit inflammation-associated bone destruction and osteoporosis.
authors: Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Su-Jin
authors: SJ
authors: Moon
authors: Inhye E
authors: IE
authors: Ahn
authors: Hyerin
authors: H
authors: Jung
authors: Hyoju
authors: H
authors: Yi
authors: Juryun
authors: J
authors: Kim
authors: Youngkyun
authors: Y
authors: Kim
authors: Seung-Ki
authors: SK
authors: Kwok
authors: Kyung-Su
authors: KS
authors: Park
authors: Jun-Ki
authors: JK
authors: Min
authors: Sung-Hwan
authors: SH
authors: Park
authors: Ho-Youn
authors: HY
authors: Kim
authors: Ji Hyeon
authors: JH
authors: Ju
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D008156:Luciferases
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