1. E74-Like Factor (ELF3) and Leptin, a Novel Loop Between Obesity and Inflammation Perpetuating a Pro-Catabolic State in Cartilage.
- Author
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Conde J, Otero M, Scotece M, Abella V, Gómez R, López V, Pino J, Mera A, Goldring MB, and Gualillo O
- Subjects
- Cartilage immunology, Cartilage metabolism, Cell Line, Cells, Cultured, Chondrocytes immunology, DNA-Binding Proteins immunology, Humans, Inflammation immunology, Interleukin-1beta immunology, Leptin genetics, Obesity immunology, Promoter Regions, Genetic, Proto-Oncogene Proteins c-ets immunology, RNA Interference, RNA, Messenger genetics, RNA, Small Interfering genetics, Receptors, Leptin genetics, Receptors, Leptin immunology, Transcription Factors immunology, Transcriptional Activation, Chondrocytes metabolism, DNA-Binding Proteins genetics, Gene Expression Regulation, Inflammation genetics, Leptin immunology, Obesity genetics, Proto-Oncogene Proteins c-ets genetics, Transcription Factors genetics
- Abstract
Background/aims: The E74-like factor 3 (ELF3) is an inflammatory mediator that participates in cartilage destruction in osteoarthritis. Leptin and other adipokines negatively impact articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. Here, we investigated whether leptin induces ELF3 expression in chondrocytes and the signaling pathway involved in this process., Methods: We determined mRNA and protein levels of ELF3 by RT-qPCR and Western blotting using cultured human primary chondrocytes and the human T/C-28a2 chondrocyte cell line. Further, we measured luciferase activities of different reporter constructs, and we assessed the contribution of leptin to the induction of ELF3 mRNA by knocking down hLEPR gene expression using siRNA technology., Results: Leptin synergizes with IL-1β in inducing ELF3 expression in chondrocytes. We also found that PI3K, p38, and JAK2 signaling pathways are at play in the leptin-driven induction of ELF3. Moreover, we confirm the participation of NFΚB in the leptin/IL-1β synergistic induction of ELF3., Conclusion: Here we show, for the first time, the regulation of ELF3 expression by leptin, suggesting that this transcription factor likely mediates the inflammatory responses triggered by leptin in articular chondrocytes., (© 2018 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2018
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