title: The critical role of IL-34 in osteoclastogenesis.
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 bone metabolism in addition to their role in the treatment of inflammatory diseases.
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland. zchen@utu.fi
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Kalman
authors.initials: K
authors.lastname: Buki
authors.forename: Jukka
authors.initials: J
authors.lastname: Vääräniemi
authors.forename: Guoliang
authors.initials: G
authors.lastname: Gu
authors.forename: H Kalervo
authors.initials: HK
authors.lastname: Väänänen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D053245:RANK Ligand / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
chemical_list: D007378:Interleukins; D053245:RANK Ligand; C552364:interleukin-34, mouse