RANKL-induced schlafen2 is a positive regulator of osteoclastogenesis

Na Kyung Lee, Han Kyung Choi, Hyun Joo Yoo, Jihye Shin, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 languageEnglish
Pages (from-to)2302-2308
Number of pages7
JournalCellular Signalling
Volume20
Issue number12
DOIs
StatePublished - Dec 2008

Keywords

  • Bone homeostasis
  • c-Jun
  • NFATc1
  • Osteoclastogenesis
  • Osteoclasts
  • RANKL

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