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E74-Like Factor (ELF3) and Leptin, a Novel Loop Between Obesity and Inflammation Perpetuating a Pro-Catabolic State in Cartilage
- Source :
- Cellular Physiology and Biochemistry, Vol 45, Iss 6, Pp 2401-2410 (2018)
- Publication Year :
- 2018
- Publisher :
- Cell Physiol Biochem Press GmbH & Co KG, 2018.
-
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.
- Subjects :
- 0301 basic medicine
Leptin
Transcriptional Activation
Physiology
Interleukin-1beta
Adipokine
Inflammation
Transcriptional control
lcsh:Physiology
Cell Line
lcsh:Biochemistry
03 medical and health sciences
Chondrocytes
Adipokines
Gene expression
medicine
Humans
lcsh:QD415-436
Obesity
RNA, Messenger
RNA, Small Interfering
Promoter Regions, Genetic
Transcription factor
PI3K/AKT/mTOR pathway
Cells, Cultured
Proto-Oncogene Proteins c-ets
lcsh:QP1-981
Chemistry
Cartilage
digestive, oral, and skin physiology
Cell biology
DNA-Binding Proteins
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Receptors, Leptin
RNA Interference
medicine.symptom
Signal transduction
hormones, hormone substitutes, and hormone antagonists
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 14219778 and 10158987
- Volume :
- 45
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cellular Physiology and Biochemistry
- Accession number :
- edsair.doi.dedup.....4cdc9860c71342ea0f878b790f9fa5c4