Pannexin 3 inhibits proliferation of osteoprogenitor cells by regulating Wnt and p21 signaling

Masaki Ishikawa, Tsutomu Iwamoto, Satoshi Fukumoto, Yoshihiko Yamada

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Canonical Wnt signaling and BMP promote the proliferation and differentiation of osteoprogenitors, respectively. However, the regulatory mechanism involved in the transition from proliferation to differentiation is unclear. Here, we show that Panx3 (pannexin 3) plays a key role in this transition by inhibiting the proliferation and promoting the cell cycle exit. Using primary calvarial cells and explants, C3H10T1/2 cells, and C2C12 cells, we found that Panx3 expression inhibited cell growth, whereas the inhibition of endogenous Panx3 expression increased it. We also found that the Panx3 hemichannel inhibited cell growth by promoting β-catenin degradation through GSK3β activation. Additionally, the Panx3 hemichannel inhibited cyclin D1 transcription and Rb phosphorylation through reduced cAMP/PKA/CREB signaling. Furthermore, the Panx3 endoplasmic reticulum Ca2+ channel induced the transcription and phosphorylation of p21, through the calmodulin/Smad pathway, and resulted in the cell cycle exit. Our results reveal that Panx3 is a new regulator that promotes the switch from proliferation to differentiation of osteoprogenitors via multiple Panx3 signaling pathways.

Original languageEnglish
Pages (from-to)2839-2851
Number of pages13
JournalJournal of Biological Chemistry
Volume289
Issue number5
DOIs
Publication statusPublished - 2014 Jan 31

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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