RRC ID 52558
Author Li C, Zheng Z, Zhang X, Asatrian G, Chen E, Song R, Culiat C, Ting K, Soo C.
Title Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes.
Journal Int J Mol Sci
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.
Volume 19(1)
Published 2018-1-6
DOI 10.3390/ijms19010168
PII ijms19010168
PMID 29316655
PMC PMC5796117
MeSH Adipose Tissue / cytology Animals Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism Calcium-Binding Proteins / pharmacology* Cell Differentiation / drug effects Cells, Cultured Chondrocytes / cytology Chondrocytes / metabolism Chondrogenesis / drug effects Core Binding Factor Alpha 1 Subunit / deficiency Core Binding Factor Alpha 1 Subunit / genetics Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors Core Binding Factor Alpha 2 Subunit / genetics Core Binding Factor Alpha 2 Subunit / metabolism Core Binding Factor Alpha 3 Subunit / genetics Core Binding Factor Alpha 3 Subunit / metabolism* Glycoproteins / genetics Glycoproteins / metabolism Glycoproteins / pharmacology* Mice Mice, Knockout NFATC Transcription Factors / antagonists & inhibitors NFATC Transcription Factors / genetics NFATC Transcription Factors / metabolism* Promoter Regions, Genetic Protein Binding RNA Interference RNA, Small Interfering / metabolism Signal Transduction / drug effects Up-Regulation / drug effects*
IF 4.556
Times Cited 2
Human and Animal Cells ATDC5(RCB0565)