학술논문

Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes.
Document Type
article
Source
International journal of molecular sciences. 19(1)
Subject
Adipose Tissue
Cells
Cultured
Chondrocytes
Animals
Mice
Knockout
Mice
Glycoproteins
Calcium-Binding Proteins
RNA
Small Interfering
Signal Transduction
Cell Differentiation
RNA Interference
Up-Regulation
Protein Binding
Chondrogenesis
Core Binding Factor Alpha 1 Subunit
Core Binding Factor Alpha 2 Subunit
Core Binding Factor Alpha 3 Subunit
NFATC Transcription Factors
Promoter Regions
Genetic
chondrogenesis
neural EGFL like 1
nuclear factor of activated T-cells 1
runt-related transcription factor 3
Chemical Physics
Other Chemical Sciences
Genetics
Other Biological Sciences
Language
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.