Dual-specificity tyrosine phosphorylation-regulated kinase 2 regulates osteoclast fusion in a cell heterotypic manner

Gali Guterman-Ram, Milena Pesic, Ayelet Orenbuch, Tal Czeiger, Anastasia Aflalo, Noam Levaot

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Monocyte fusion into osteoclasts, bone resorbing cells, plays a key role in bone remodeling and homeostasis; therefore, aberrant cell fusion may be involved in a variety of debilitating bone diseases. Research in the last decade has led to the discovery of genes that regulate osteoclast fusion, but the basic molecular and cellular regulatory mechanisms underlying the fusion process are not completely understood. Here, we reveal a role for Dyrk2 in osteoclast fusion. We demonstrate that Dyrk2 down regulation promotes osteoclast fusion, whereas its overexpression inhibits fusion. Moreover, Dyrk2 also promotes the fusion of foreign-body giant cells, indicating that Dyrk2 plays a more general role in cell fusion. In an earlier study, we showed that fusion is a cell heterotypic process initiated by fusion-founder cells that fuse to fusion-follower cells, the latter of which are unable to initiate fusion. Here, we show that Dyrk2 limits the expansion of multinucleated founder cells through the suppression of the fusion competency of follower cells.

Original languageEnglish
Pages (from-to)617-629
Number of pages13
JournalJournal of Cellular Physiology
Volume233
Issue number1
DOIs
StatePublished - 1 Jan 2018

Keywords

  • Dyrk2
  • cell fusion
  • heterotypic fusion
  • osteoclast
  • osteoclast fusion

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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