Abstract
Osteoclasts are hematopoietic lineage derived-multinucleated cells that resorb bone. Their activity in balance with that of osteoblast is essential for bone homeostasis. Receptor activator of NF-κB ligand (RANKL) is known as an essential cytokine for the osteoclastogenesis, and c-Jun signaling in cooperation with NFAT family is crucial for RANKL-regulated osteoclastogenesis. We show here that schlafen2 (Slfn2), a member of a new family of growth regulatory genes involved in thymocyte development, is critical for osteoclastogenesis. RANKL selectively induces Slfn2 expression in osteoclast precursors via Rac1 signaling pathway. Targeted inhibition of Slfn2 by small interfering RNAs (siRNAs) markedly inhibits the formation of osteoclasts by diminishing the activation of c-Jun and the expression of c-Jun and NFATc1. In contrast, the overexpression of Slfn2 markedly increased phosphorylation and transactivation of c-Jun by RANKL. Together, these results indicate that Slfn2 has an essential role in osteoclastogenesis, functioning upstream of c-Jun and NFATc1.
Original language | English |
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Pages (from-to) | 2302-2308 |
Number of pages | 7 |
Journal | Cellular Signalling |
Volume | 20 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2008 |
Bibliographical note
Funding Information:We thank Dr. Toshio Kitamura for providing the Plat-E cell line and a retroviral vector, pMX-IRES-EGFP, Dr. Hedrick S. for providing pCIN-4-Slfn2 plasmid, Dr. Prywes R. for providing a c-Jun promoter reporter, pJC6GL3, Dr. Serfling E. for providing the reporter plasmid pNFATc1P1-0.8 kb-luc, and Dr. Kim J. for critically reading the manuscript. This work was supported in part by the Korea Science and Engineering Foundation (KOSEF) NRL Program grant funded by the Korea government (MEST) (No. R0A-2008-000-20001-0), by the KOSEF grant (No. M1-0641-35-0002; R01-2007-000-20141-0), and by the NCRC program (R15-2006-020) of KOSEF through the Center for Cell Signaling and Drug Discovery Research at Ewha Womans University. N.L., H.C., and J.S. were supported by the BK21 Project.
Keywords
- Bone homeostasis
- c-Jun
- NFATc1
- Osteoclastogenesis
- Osteoclasts
- RANKL