Interleukin-34 is expressed by giant cell tumours of bone and plays a key role in RANKL-induced osteoclastogenesis
| Autor: | Anne Riet, Dominique Heymann, Marc Baud'huin, Romain Renault, Céline Charrier, François Gouin, Régis Brion, Laurence Duplomb, Anne Moreau |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
musculoskeletal diseases
MAPK/ERK pathway Adult Male Pathology medicine.medical_specialty Stromal cell Histology Cell Survival Physiology medicine.medical_treatment Endocrinology Diabetes and Metabolism Osteoclasts Bone Neoplasms Receptor Macrophage Colony-Stimulating Factor Anisoles Mice Young Adult Osteoclast medicine Cell Adhesion Animals Humans Progenitor cell Bone Resorption Protein kinase B Cells Cultured Aged Cell Proliferation CD11b Antigen biology Dose-Response Relationship Drug Chemistry Interleukins RANK Ligand Carcinoma Giant Cell Middle Aged Neoplasm Proteins Mice Inbred C57BL medicine.anatomical_structure Cytokine Pyrimidines RANKL Interleukin 34 biology.protein Cancer research Female Signal Transduction |
| Zdroj: | Bone. 46:S62-S63 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/j.bone.2010.01.149 |
| Popis: | Interleukin-34 (IL-34) is a newly discovered regulator of myeloid lineage differentiation, proliferation, and survival, acting via the macrophage-colony stimulating factor receptor (M-CSF receptor, c-fms). M-CSF, the main ligand for c-fms, is required for osteoclastogenesis and has been already identified as a critical contributor of the pathogenesis of giant cell tumours of bone (GCTs), tumours rich in osteoclasts. According to the key role of M-CSF in osteoclastogenesis and GCTs, the expression of IL-34 in human GCTs was first assessed. Quantitative analysis of IL-34 mRNA expression in 14 human GCTs revealed expression of this cytokine in GCTs as well as M-CSF and c-fms. Immunohistochemistry demonstrated that osteoclast-like cells exhibited a huge immunostaining for IL-34 and that mononuclear stromal cells were slightly positive for this protein. In contrast to osteoblasts, bone-resorbing osteoclasts showed very strong staining for IL-34, suggesting its potential role in the pathogenesis of GCTs by facilitating osteoclast formation. The role of IL-34 in osteoclastogenesis was then studied in murine and human models. IL-34 was able to support RANKL-induced osteoclastogenesis in the absence of M-CSF in all models. Multinucleated cells generated in the presence of IL-34 and RANKL expressed specific osteoclastic markers and resorbed dentine. IL-34 induced phosphorylation of ERK 1/2 and Akt through the activation of c-fms, as revealed by the inhibition of signalling by a specific c-fms tyrosine kinase inhibitor. Furthermore, IL-34 stimulated RANKL-induced osteoclastogenesis by promoting the adhesion and proliferation of osteoclast progenitors, and had no effect on osteoclast survival. Overall, these data reveal that IL-34 can be entirely substituted for M-CSF in RANKL-induced osteoclastogenesis, thus identifying a new biological activity for this cytokine and a contribution to the pathogenesis of GCTs. |
| Databáze: | OpenAIRE |
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