E74-Like Factor (ELF3) and Leptin, a Novel Loop Between Obesity and Inflammation Perpetuating a Pro-Catabolic State in Cartilage

被引:16
作者
Conde, Javier [1 ]
Otero, Miguel [2 ,3 ]
Scotece, Morena [1 ]
Abella, Vanessa [1 ]
Gomez, Rodolfo [4 ]
Lopez, Veronica [1 ]
Pino, Jesus [5 ]
Mera, Antonio [6 ]
Goldring, Mary B. [2 ,3 ]
Gualillo, Oreste [1 ]
机构
[1] Santiago Univ, Clin Hosp, NEIRID Lab NeuroEndocrine Interact Rheumatol & In, SERGAS,Inst Med Res IDIS, Bldg C,Level-2, Santiago De Compostela, Spain
[2] Weill Cornell Med Coll, Hosp Special Surg, Orthopaed Soft Tissue Res Program, New York, NY USA
[3] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA
[4] Santiago Univ, Clin Hosp, Inst IDIS, Musculoskeletal Pathol Lab, Santiago De Compostela, Spain
[5] Santiago Univ, Clin Hosp, Div Orthopaed Surg & Traumatol, SERGAS, Santiago De Compostela, Spain
[6] Santiago Univ, Clin Hosp, Div Rheumatol, SERGAS Serv Galego Saude, Santiago De Compostela, Spain
基金
美国国家卫生研究院; 欧盟地平线“2020”;
关键词
Adipokines; Transcriptional control; Inflammation; Cartilage; SYNTHASE TYPE-II; TRANSCRIPTION FACTOR ESE-1; NITRIC-OXIDE; HUMAN CHONDROCYTES; OSTEOARTHRITIC CARTILAGE; SYNOVIAL-FLUID; JOINT TISSUES; KAPPA-B; EXPRESSION; CELLS;
D O I
10.1159/000488227
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-1 beta 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 NF kappa B in the leptin/IL-1 beta 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. (C) 2018 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:2401 / 2410
页数:10
相关论文
共 36 条
[1]   Modulation of ICAM-1 expression in ECV304 cells by macrophage-released cytokines [J].
Antonelli, A ;
Bianchi, M ;
Crinelli, R ;
Gentilini, L ;
Magnani, M .
BLOOD CELLS MOLECULES AND DISEASES, 2001, 27 (06) :978-991
[2]   Leptin: A Critical Regulator of CD4+ T-cell Polarization in Vitro and in Vivo [J].
Batra, Arvind ;
Okur, Besir ;
Glauben, Rainer ;
Erben, Ulrike ;
Ihbe, Jakob ;
Stroh, Thorsten ;
Fedke, Inka ;
Chang, Hyun-Dong ;
Zeitz, Martin ;
Siegmund, Britta .
ENDOCRINOLOGY, 2010, 151 (01) :56-62
[3]   Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!) [J].
Berenbaum, F. .
OSTEOARTHRITIS AND CARTILAGE, 2013, 21 (01) :16-21
[4]   E74-like factor 3 and nuclear factor-B regulate lipocalin-2 expression in chondrocytes [J].
Conde, Javier ;
Otero, Miguel ;
Scotece, Morena ;
Abella, Vanessa ;
Lopez, Veronica ;
Pino, Jesus ;
Gomez, Rodolfo ;
Lago, Francisca ;
Goldring, Mary B. ;
Gualillo, Oreste .
JOURNAL OF PHYSIOLOGY-LONDON, 2016, 594 (21) :6133-6146
[5]   IL-36α: a novel cytokine involved in the catabolic and inflammatory response in chondrocytes [J].
Conde, Javier ;
Scotece, Morena ;
Abella, Vanessa ;
Lois, Ana ;
Lopez, Veronica ;
Garcia-Caballero, Tomas ;
Pino, Jesus ;
Jesus Gomez-Reino, Juan ;
Gomez, Rodolfo ;
Lago, Francisca ;
Gualillo, Oreste .
SCIENTIFIC REPORTS, 2015, 5
[6]  
Conde J, 2013, DISCOV MED, V15, P73
[7]   Adiponectin and Leptin Induce VCAM-1 Expression in Human and Murine Chondrocytes [J].
Conde, Javier ;
Scotece, Morena ;
Lopez, Veronica ;
Gomez, Rodolfo ;
Lago, Francisca ;
Pino, Jesus ;
Gomez-Reino, Jesus ;
Gualillo, Oreste .
PLOS ONE, 2012, 7 (12)
[8]  
Felson DT, 2005, J RHEUMATOL, V32, P1133
[9]   ROLES OF INFLAMMATORY AND ANABOLIC CYTOKINES IN CARTILAGE METABOLISM: SIGNALS AND MULTIPLE EFFECTORS CONVERGE UPON MMP-13 REGULATION IN OSTEOARTHRITIS [J].
Goldring, Mary B. ;
Otero, Miguel ;
Plumb, Darren A. ;
Dragomir, Cecilia ;
Favero, Marta ;
El Hachem, Karim ;
Hashimoto, Ko ;
Roach, Helmtrud I. ;
Olivotto, Eleonora ;
Borzi, Rosa Maria ;
Marcu, Kenneth B. .
EUROPEAN CELLS & MATERIALS, 2011, 21 :202-220
[10]   INTERLEUKIN-1-BETA-MODULATED GENE-EXPRESSION IN IMMORTALIZED HUMAN CHONDROCYTES [J].
GOLDRING, MB ;
BIRKHEAD, JR ;
SUEN, LF ;
YAMIN, R ;
MIZUNO, S ;
GLOWACKI, J ;
ARBISER, JL ;
APPERLEY, JF .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (06) :2307-2316