Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version


Publication Source

International Journal of Molecular Sciences





Start Page

Article number 168




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.


At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.


Chondrogenesis, 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



Date Posted: 10 February 2023