Javier Conde1, Miguel Otero2, Morena Scotece1, Vanessa Abella1, Rodolfo Gómez3, Verónica López1, Jesús Pino4, Antonio Mera5, Mary B Goldring2, Oreste Gualillo1. 1. SERGAS, Santiago University Clinical Hospital, NEIRID Lab (NeuroEndocrine Interaction in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Building C, Level-2, Santiago de Compostela, Spain. 2. Orthopaedic Soft Tissue Research Program, The Hospital for Special Surgery, and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA. 3. Musculoskeletal Pathology Laboratory, Institute IDIS, Santiago University Clinical Hospital, Santiago de Compostela, Spain. 4. SERGAS, Santiago University Clinical Hospital, Division of Orthopaedic Surgery and Traumatology, Santiago de Compostela, Spain. 5. SERGAS (Servizo Galego de Saude), Division of Rheumatology, Santiago University Clinical Hospital, Santiago de Compostela, Spain.
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.
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.
Authors: Alfonso Cordero-Barreal; María González-Rodríguez; Clara Ruiz-Fernández; Djedjiga Ait Eldjoudi; Yousof Ramadan Farrag AbdElHafez; Francisca Lago; Javier Conde; Rodolfo Gómez; Miguel Angel González-Gay; Ali Mobasheri; Jesus Pino; Oreste Gualillo Journal: Int J Mol Sci Date: 2021-02-27 Impact factor: 5.923