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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Reciprocal regulation of Notch and nuclear factor of activated T-cells (NFAT) c1 transactivation in osteoblasts

Stefano Zanotti1, Anna Smerdel-Ramoya, Ernesto Canalis

  • 1Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.

The Journal of Biological Chemistry
|December 7, 2010
PubMed

Insights

Notch and NFAT signaling pathways reciprocally inhibit each other in osteoblasts. This interaction forms a regulatory network controlling cell fate determination and differentiation, crucial for bone biology.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Notch signaling dictates cell fate, while Nuclear Factor of Activated T-cells (NFAT)c regulates cell differentiation.
  • Understanding the interplay between Notch and NFAT is crucial for comprehending osteoblast biology.

Purpose of the Study:

  • To investigate the interaction between Notch and NFAT signaling pathways in osteoblastic cells.
  • To elucidate the functional consequences of this interaction on osteoblast differentiation and gene expression.

Main Methods:

  • Notch signaling activated using Notch1 intracellular domain (NICD) vectors and Cre-mediated recombination.
  • NFATc1 activated via adenoviral vectors expressing constitutively active NFATc1.
  • Assessed pathway crosstalk using gene expression analysis, DNA binding assays, co-immunoprecipitation, and confocal microscopy.

Main Results:

  • Notch signaling inhibited NFAT transactivation and NFATc1 transcription.
  • NFATc1 suppressed Notch target gene transactivation and competed with CSL for DNA binding.
  • Both NICD and NFATc1 inhibited osteoblast marker gene expression; NICD alone suppressed osteoblastic lineage commitment.

Conclusions:

  • Notch1 intracellular domain (NICD) and NFATc1 signaling pathways exhibit reciprocal inhibition.
  • A regulatory network involving NICD and NFATc1 controls osteoblast activity and differentiation.
  • This crosstalk is a key mechanism in regulating bone cell function.

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