Involvement of Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts
| Autor: | Michio Tomura, Masaru Ishii, Yongwon Choi, Noriko Takegahara, Hyunsoo Kim, Atsushi Miyawaki, Asako Sakaue-Sawano, Hiroki Mizuno, Osami Kanagawa |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
cell division
Male 0301 basic medicine Cell division Osteoclasts Osteolysis Biochemistry Cell Fusion 0302 clinical medicine Osteogenesis Phosphorylation Cells Cultured Cell fusion biology imaging food and beverages pathological conditions signs and symptoms Cell cycle Cell biology medicine.anatomical_structure RANKL 030220 oncology & carcinogenesis osteoclast musculoskeletal diseases Recombinant Fusion Proteins Bone Marrow Cells Mice Transgenic Polyploidy 03 medical and health sciences Multinucleate Osteoclast Quinoxalines medicine Animals Molecular Biology Crosses Genetic Myeloid Progenitor Cells Cytokinesis Cell Nucleus incomplete cytokinesis Cell growth flow cytometry RANK Ligand fungi Cell Biology Luminescent Proteins cell proliferation 030104 developmental biology biology.protein Cancer research Benzimidazoles Protein Processing Post-Translational Proto-Oncogene Proteins c-akt Biomarkers |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.677427 |
| Popis: | Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-κB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. |
| Databáze: | OpenAIRE |
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