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Objective: Lipocalin-2 (LCN2) is an adipokine that was first identified in neutrophil granules. In the last years it was recognized as a factor that could impair chondrocyte phenotype, cartilage homeostasis as well as growth plate development. Both pro-inflammatory cytokines and glucocorticoids (GCs) modulate LCN2 expression. Actually, GCs were found to be LCN2 inducers, suggesting that part of the negative actions exerted by these anti-inflammatory drugs at cartilage level could be mediated by this adipokine. So, in this study we wanted to investigate whether corticoids were able to act in synergy with IL-1 in the induction of LCN2 and the signaling pathway involved in this process., Materials and Methods: For the realization of this work, ATDC5 mouse chondrogenic cell line was used. We determined the mRNA and protein expression of LCN2 by real-time reverse transcription-polymerase chain reaction (RT-qPCR) and western blot respectively, after GC or mineralcorticoid treatment. Different signaling pathways inhibitors were also used., Results: GC and mineralcorticoid were able to induce the expression of LCN2 in ATDC5 cells. Interestingly, both corticoids synergized with IL-1 in the induction of LCN2. The effect of these corticoids on the expression of LCN2 occurred through GC or mineralcorticoid receptors and the kinases PI3K, ERK1/2 and JAK2., Conclusions: Prolonged use of corticoids may have detrimental effects on cartilage homeostasis. Based on our results, we conclude that corticoids could increase the negative actions exerted by IL-1 by increasing the expression of LCN2., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) is a chronic systemic musculoskeletal disorder involving inflammation, immunity, and metabolic alterations. OA is commonly regarded as non-inflammatory disease; still inflammation is recognized as contributing to the symptoms and progression of OA. New evidence suggests that adipokines are involved in the pathophysiology of OA and might modulate the production of inflammatory mediators including in immune cells. However, the role of immune component in osteoarthritis is still poorly investigated. To gain further insights into the interaction of immune cells in OA and the role of adipokines on these cells, we performed experiments aimed to determine the cytokine profile in activated CD4 + T cells from OA patients. For completeness, we also explored the cross talk between T lymphocytes and chondrocytes in OA by co-culturing human primary chondrocytes with activated CD4 + T cells in two ways: the first by incubating the cells by direct contact (D.C.) or by transwell system. Our results show that the exposure of activated CD4 + T cells to adipokines modulates IL-6, IL-8, and CCL-3 production. In addition, the production of key macromolecules of ECM (aggrecan and collagen-2) and matrix metalloproteinase 13 (MMP-13) in co-cultured chondrocytes with activated CD4 + T cells was altered. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1299-1303, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Key Points: E74-like factor 3 (ELF3) is a transcription factor regulated by inflammation in different physio-pathological situations. Lipocalin-2 (LCN2) emerged as a relevant adipokine involved in the regulation of inflammation. In this study we showed for the first time the involvement of ELF3 in the control of LCN2 expression and its cooperation with nuclear factor-κB (NFκB). Our results will help to better understand of the role of ELF3, NFκB and LCN2 in the pathophysiology of articular cartilage., Abstract: E74-like factor 3 (ELF3) is a transcription factor induced by inflammatory cytokines in chondrocytes that increases gene expression of catabolic and inflammatory mediators. Lipocalin 2 (LCN2) is a novel adipokine that negatively impacts articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. Here, we investigated the control of LCN2 gene expression by ELF3 in the context of interleukin 1 (IL-1)-driven inflammatory responses in chondrocytes. The interaction of ELF3 and nuclear factor-κB (NFκB) in modulating LCN2 levels was also explored. LCN2 mRNA and protein levels, as well those of several other ELF3 target genes, were determined by RT-qPCR and Western blotting. Human primary chondrocytes, primary chondrocytes from wild-type and Elf3 knockout mice, and immortalized human T/C-28a2 and murine ATDC5 cell lines were used in in vitro assays. The activities of various gene reporter constructs were evaluated by luciferase assays. Gene overexpression and knockdown were performed using specific expression vectors and siRNA technology, respectively. ELF3 overexpression transactivated the LCN2 promoter and increased the IL-1-induced mRNA and protein levels of LCN2, as well as the mRNA expression of other pro-inflammatory mediators, in human and mouse chondrocytes. We also identified a collaborative loop between ELF3 and NFκB that amplifies the induction of LCN2. Our findings show a novel role for ELF3 and NFκB in the induction of the pro-inflammatory adipokine LCN2, providing additional evidence of the interaction between ELF3 and NFκB in modulating inflammatory responses, and a better understanding of the mechanisms of action of ELF3 in chondrocytes., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)