Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes
Penn collection
Degree type
Discipline
Subject
Neural EGFL like 1 (Nell-1)
Nuclear factor of activated T-cells 1 (Nfatc1)
Runt-related transcription factor 3 (Runx3)
Adipose Tissue
Animals
Calcium-Binding Proteins
Cell Differentiation
Cells
Cultured
Chondrocytes
Chondrogenesis
Core Binding Factor Alpha 1 Subunit
Core Binding Factor Alpha 2 Subunit
Core Binding Factor Alpha 3 Subunit
Glycoproteins
Mice
Mice
Knockout
NFATC Transcription Factors
Promoter Regions
Genetic
Protein Binding
RNA Interference
RNA
Small Interfering
Signal Transduction
Up-Regulation
neural egfl like 1
nucleic acid binding protein
protein Patched 1
scleroprotein
short hairpin RNA
transcription factor FOXP1
transcription factor FOXP2
transcription factor NFAT
transcription factor NFAT5
transcription factor RUNX1
transcription factor RUNX3
transcription factor Sox1
transcription factor Sox10
transcription factor Sox2
transcription factor Sox8
transcription factor Sox9
unclassified drug
calcium binding protein
glycoprotein
Nell1 protein
mouse
protein binding
Runx1 protein
mouse
Runx2 protein
mouse
Runx3 protein
mouse
small interfering RNA
transcription factor NFAT
transcription factor RUNX1
transcription factor RUNX2
transcription factor RUNX3
animal cell
animal experiment
Article
binding site
bioinformatics
cell differentiation
chondrocyte
chondrogenesis
chromatin immunoprecipitation
controlled study
gene expression
gene silencing
immunofluorescence test
mouse
newborn
nonhuman
promoter region
real time polymerase chain reaction
RNA interference
signal transduction
upregulation
adipose tissue
animal
antagonists and inhibitors
cell culture
chondrocyte
cytology
deficiency
drug effect
genetics
knockout mouse
metabolism
upregulation
Dental Materials
Dentistry
Orthodontics and Orthodontology
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Abstract
Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1‘s pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear factor of activated T-cells 1 (Nfatc1) as the key transcriptional factor mediating the Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, we were able to determine that Nfatc1 binds to the -833--810 region of the Runx3-promoter in response to Nell-1 treatment. By revealing the Nell-1 → Nfatc1 → Runx3→Ihh cascade, we demonstrate the involvement of Nfatc1, a nuclear factor of activated T-cells, in chondrogenesis, while providing innovative insights into developing a novel therapeutic strategy for cartilage regeneration and other chondrogenesis-related conditions. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.