Involvement of receptor activator of nuclear factor-κB ligand (RANKL)-induced incomplete cytokinesis in the polyploidization of osteoclasts

Noriko Takegahara, Hyunsoo Kim, Hiroki Mizuno, Asako Sakaue-Sawano, Atsushi Miyawaki, Michio Tomura, Osami Kanagawa, Masaru Ishii, Yongwon Choi

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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 cytokinesishad 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.

Original languageEnglish
Pages (from-to)3439-3454
Number of pages16
JournalJournal of Biological Chemistry
Volume291
Issue number7
DOIs
Publication statusPublished - 12-02-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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