Ciliary IFT80 regulates dental pulp stem cells differentiation by FGF/FGFR1 and Hh/BMP2 signaling

Xue Yuan, Min Liu, Xu Cao, Shuying Yang

Research output: Contribution to journalArticle

Abstract

Primary cilia and intraflagellar transport (IFT) proteins control a wide variety of processes during development and tissue homeostasis. However, their potential roles in the regulation of stem cell differentiation and tooth development remain elusive. Here, we uncovered the critical roles of ciliary IFT80 in cilia formation and differentiation of dental pulp stem cells (DPSCs). IFT80-deficient DPSCs showed reduced fibroblast growth factor receptor 1 (FGFR1) expression, leading to the disruption of FGF2–FGFR1 signaling. We found, during DPSC differentiation, FGF2-FGFR1 signaling induces stress fiber rearrangement to promote cilia elongation, meanwhile stimulates PI3K-AKT signaling to aid Hh/bone morphogenetic protein 2 (BMP2) signaling activation. These signaling pathways and their coupling were disrupted in IFT80-deficient DPSCs, causing impaired differentiation. Our findings revealed a novel mechanism that ciliary protein regulates the odontogenic differentiation of DPSCs through FGF/FGFR1 and Hh/BMP2 signaling.

Original languageEnglish (US)
Pages (from-to)2087-2099
Number of pages13
JournalInternational Journal of Biological Sciences
Volume15
Issue number10
DOIs
StatePublished - Jan 1 2019

Keywords

  • Bone morphogenetic protein
  • Dental pulp stem cells
  • Fibroblast growth factor signaling
  • Hedgehog signaling
  • Intraflagellar transport
  • Primary cilia

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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