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

研究成果: Article査読

19 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3439-3454
ページ数16
ジャーナルJournal of Biological Chemistry
291
7
DOI
出版ステータスPublished - 12-02-2016
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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