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A proposed mechanism of the inhibitory action of IL-18 on osteoclast differentiation

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posted on 2011-12-30, 22:12 authored by Nobuyuki Udagawa, Shigeru Kotake, Naoyuki Kamatani, Naoyuki Takahashi, Tatsuo Suda

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Taken from "The molecular mechanism of osteoclastogenesis in rheumatoid arthritis"

Arthritis Research 2002;4(5):281-289.

Published online 12 Apr 2002

PMCID:PMC128939.

IL-18 secreted from osteoblasts acts on T lymphocytes, which generate granulocyte–macrophage colony-stimulating factor (GM-CSF) and IFN-γ. Both GM-CSF and IFN-γ are potent inhibitors of osteoclast formation, at least . When GM-CSF binds its receptor, GM-CSFR (present in osteoclast progenitors), osteoclast formation is completely inhibited. In contrast, the target molecule of IFN-γ is TNF receptor-associated factor 6 (TRAF6). The degradation of TRAF6 by IFN-γ leads to the inhibition of osteoclastogenesis. The inhibitory action of IL-18 on osteoclast differentiation occurs via GM-CSF, but not via IFN-γ.