Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
NellOne Therapeutics, Inc., 99 Midway Ln # E, Oak Ridge, TN 37830, USA.
Int J Mol Sci. 2018 Jan 6;19(1):168. doi: 10.3390/ijms19010168.
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 -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.
神经 EGFL 样蛋白 1（Nell-1）对于软骨细胞的分化、成熟和再生是必不可少的。我们之前的研究表明，Nell-1 的促软骨形成活性主要依赖于 runt 相关转录因子 3（Runx3）介导的印度刺猬（Ihh）信号。在这里，我们确定激活 T 细胞的核因子 1（Nfatc1）是介导Nell-1→软骨细胞中 Runx3 信号转导的关键转录因子。通过染色质免疫沉淀试验，我们能够确定 Nfatc1 结合到响应 Nell-1 处理的-β 启动子的-833--810 区域。通过揭示 Nell-1→Nfatc1→Runx3→Ihh 级联反应，我们证明了激活 T 细胞的核因子 Nfatc1 参与了软骨生成，同时为开发软骨再生和其他与软骨生成相关的条件的新的治疗策略提供了新的见解。
