Dual-specificity tyrosine phosphorylation-regulated kinase 2 regulates osteoclast fusion in a cell heterotypic manner.
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.
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Gali
G
Guterman-Ram
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Milena
M
Pesic
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Ayelet
A
Orenbuch
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Tal
T
Czeiger
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Anastasia
A
Aflalo
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Regenerative Medicine and Stem Cell (RMSC) Research Center, Beer-Sheva, Israel.
Noam
http://orcid.org/0000-0001-7747-3883
N
Levaot
D000818:Animals; D001862:Bone Resorption; D002454:Cell Differentiation; D002459:Cell Fusion; D049109:Cell Proliferation; D015971:Gene Expression Regulation, Enzymologic; D015743:Giant Cells, Foreign-Body / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D000097603:Dyrk Kinases
D050778:NFATC Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D000097603:Dyrk Kinases; C494005:Nfatc1 protein, mouse
Dyrk2; cell fusion; heterotypic fusion; osteoclast; osteoclast fusion