the critical role of il-34 in osteoclastogenesis在osteoclastogenesis il-34的至关重要的作用.pdf
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The Critical Role of IL-34 in Osteoclastogenesis
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Zhi Chen * , Kalman Buki , Jukka Vaaraniemi , Guoliang Gu , H. Kalervo Vaananen
1 Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland, 2 University of Eastern Finland, Kuopio campus, Kuopio, Finland
Abstract
It has been widely believed that the cytokines required for osteoclast formation are M-CSF (also known as CSF-1) and
RANKL. Recently, a novel cytokine, designated IL-34, has been identified as another ligand of CSF1R. This study was to
explore the biological function, specifically osteoclastogenesis and bone metabolism, of the new cytokine. We produced
recombinant mouse IL-34 and found that together with RANKL it induces the formation of osteoclasts both from
splenocytes as well as dose-dependently from bone marrow cells in mouse and these cells also revealed bone resorption
activity. It also promotes osteoclast differentiation from human peripheral blood mononucleated cells. Finally, we show that
systemic administration of IL-34 to mice increases the proportion of CD11b+ cells and reduces trabecular bone mass. Our
data indicate that IL-34 is another important player in osteoclastogenesis and thus may have a role in bone diseases.
Strategies of targeting CSF1/CSF1R have been developed and some of them are already in preclinical and clinical studies for
treatment of inflammatory diseases. Our results strongly suggest the need to revisit these strategies as they may provide a
new potential pharmaceutical target for the regulation of
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