Protein inhibitor of activated STAT 3 modulates osteoclastogenesis by down-regulation of NFATc1 and osteoclast-associated receptor

Kabsun Kim, Junwon Lee, Ha Kim Jung, Mi Jin Hye, Bin Zhou, Young Lee Soo, Nacksung Kim

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Protein inhibitor of activated STAT3 (PIAS3) has been shown to regulate the activity of various transcription factors. In this study, we show that the overexpression of PIAS3 in bone marrow-derived monocyte/macrophage lineage cells attenuates osteoclast formation and down-regulates the expression of NFATc1 and osteoclast-associated receptor (OSCAR), which are important modulators in osteoclastogenesis. PIAS3 has been shown to associate with histone deacetylase 1 as well as with transcription factors, including the microphthalmia transcription factor, NFATc1, and c-Fos. Moreover, overexpression of PIAS3 inhibits the transactivation of target genes such as NFATc1 and OSCAR. This inhibitory effect of PIAS3 is possibly mediated by histone deacetylase 1 recruitment to the promoter regions of NFATc1 and OSCAR. Furthermore, silencing of PIAS3 by RNA interference in osteoclast precursors enhances osteoclast formation as well as gene expression of NFATc1 and OSCAR. Taken together, our results reveal that PIAS3 acts as a modulator in osteoclastogenesis.

Original languageEnglish (US)
Pages (from-to)5588-5594
Number of pages7
JournalJournal of Immunology
Volume178
Issue number9
DOIs
StatePublished - May 1 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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