The critical role of IL-34 in osteoclastogenesis

• Published in: PloS one 2011-04, Vol.6 (4), p.e18689-e18689
• Main Authors: Chen, Zhi, Buki, Kalman, Vääräniemi, Jukka, Gu, Guoliang, Väänänen, H Kalervo
• Format: Article
• Language: English
• Subjects: Acids; Animals; Arthritis; B cells; Biocompatibility; Biology; Bone (trabecular); Bone and Bones - drug effects; Bone and Bones - pathology; Bone diseases; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone mass; Bone resorption; Bone Resorption - pathology; Bone turnover; Cancellous bone; CD11b antigen; Cell Count; Cell Differentiation - drug effects; Cytokines; Diseases; Humans; Hypotheses; Inflammatory diseases; Interleukins - administration & dosage; Interleukins - metabolism; Interleukins - pharmacology; Ligands; Lymphocytes; Macrophage colony stimulating factor; Medical treatment; Medicine; Metabolism; Mice; Mutation; Organ Size - drug effects; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoclastogenesis; Osteoclasts; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteogenesis - drug effects; Peripheral blood; Phosphatase; Proteins; RANK Ligand - pharmacology; Spleen - cytology; Splenocytes; TRANCE protein; Tumor necrosis factor-TNF; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018689

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.