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Int. J. Mol. Sci. 2018, 19(1), 168; https://doi.org/10.3390/ijms19010168

Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes

1
Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
2
NellOne Therapeutics, Inc., 99 Midway Ln # E, Oak Ridge, TN 37830, USA
3
Division of Plastic and Reconstructive Surgery and Department of Orthopaedic Surgery, the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 4 December 2017 / Revised: 19 December 2017 / Accepted: 5 January 2018 / Published: 6 January 2018
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: neural EGFL like 1 (Nell-1); nuclear factor of activated T-cells 1 (Nfatc1); runt-related transcription factor 3 (Runx3); chondrogenesis neural EGFL like 1 (Nell-1); nuclear factor of activated T-cells 1 (Nfatc1); runt-related transcription factor 3 (Runx3); chondrogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Li, C.; Zheng, Z.; Zhang, X.; Asatrian, G.; Chen, E.; Song, R.; Culiat, C.; Ting, K.; Soo, C. Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes. Int. J. Mol. Sci. 2018, 19, 168.

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