PIASxβ is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts

Md Moksed Ali, Tatsuya Yoshizawa, Osamu Ishibashi, Akio Matsuda, Mika Ikegame, Junko Shimomura, Hisashi Mera, Kazuhisa Nakashima, Hiroyuki Kawashima

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We recently reported that tensile stress induces osteoblast differentiation and osteogenesis in the mouse calvarial suture in vitro. Using this experimental system, we identified PIASxβ, a splice isoform of Pias2, as one of the genes most highly upregulated by tensile stress. Further study using cell culture revealed that this upregulation was transient and was accompanied by upregulation of other differentiation markers, including osterix, whereas expression of Runx2 was unaffected. Runx2 and osterix are the two master proteins controlling osteoblast differentiation, with Runx2 being upstream of osterix. Targeted knockdown of PIASxβ by small interfering RNA (siRNA) markedly suppressed osteoblastic differentiation and matrix mineralization, whereas transient overexpression. of PIASxβ caused the exact opposite effects. Regardless of PIASxβ expression level, Runx2 expression remained constant. Reporter assays demonstrated that osterix enhanced its own promoter activity, which was further stimulated by PIASxβ but not by its sumoylation-defective mutant. NFATc1 and NFATc3 additionally increased osterix transcriptional activity when cotransfected with PIASxβ. Because osterix: has no consensus motif for sumoylation, other proteins are probably involved in the PIASxβ-mediated activation and NFAT proteins may be among such targets. This study provides the first line of evidence that PIASxβ is indispensable for osteoblast differentiation and matrix mineralization, and that this signaling molecule is located between Runx2 and osterix.

Original languageEnglish
Pages (from-to)2565-2573
Number of pages9
JournalJournal of cell science
Volume120
Issue number15
DOIs
Publication statusPublished - Aug 1 2007
Externally publishedYes

Keywords

  • Mineralization
  • Osteoblast
  • Osterix
  • PIASxβ

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Ali, M. M., Yoshizawa, T., Ishibashi, O., Matsuda, A., Ikegame, M., Shimomura, J., Mera, H., Nakashima, K., & Kawashima, H. (2007). PIASxβ is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts. Journal of cell science, 120(15), 2565-2573. https://doi.org/10.1242/jcs.005090