Article Text

FRI0013 Ese-1: a novel pro-inflammatory and catabolic factor in articular cartilage
  1. J. Conde1,
  2. M. Scotece1,
  3. M. Otero2,
  4. V. Lopez1,
  5. J. J. Gomez-Reino1,
  6. M. B. Goldring2,
  7. O. Gualillo1
  1. 1Research Area, Laboratory 9, Santiago University Clinical Hospital, Santiago de Compostela, Spain
  2. 2Cartilage Biology, Hospital for Special Surgery, New York, United States


Background Articular cartilage is a highly specialized connective tissue that lines bone surfaces and provides a low friction in the joint. In adult articular cartilage, chondrocytes are responsible for the turnover and maintenance of the structural and extracellular matrix. However, during cartilage degenerative diseases chondrocytes exhibit aberrant behaviour and several factors, including members of the ETS family of transcription factors, are known to regulate many different processes including inflammation.

ESE-1 is a novel member of ETS transcription factor superfamily. It is expressed in inflammatory conditions and in cartilage and synovium from osteoarthritis (OA) and rheumatoid arthritis (RA) subjects.

Objectives Despite the large body of work on ETS biology, much remains to be learned about the precise function of ESE-1 in cartilage. Thus, this work aimed to determine the possible biological action/s of ESE-1 in chondrocytes. First, we analyzed the effect of ESE-1 on the induction of several inflammatory factors such as lipocalin-2 (LCN2), nitric oxide (NO), etc, and next the signalling pathways involved in these processes. Furthermore, we investigated the impact of ESE-1 on the expression of the principal collagen type II degrading enzyme, MMP-13.

Methods We overexpressed ESE-1 using a pCI vector in human and murine chondrocytes in order to determine the effect of ESE-1 on specific target genes. Expression of ESE-1- driven genes was determined by qRT-PCR and western blot analysis. Next, to gain further insights, we analyzed the expression of LCN2 and nitric oxide in murine chondrocytes from wild type and ESE-1 knockout mice.

Results ESE-1 overexpression, when cells have been stimulated in the presence of IL-1, was able to significantly increase lipocalin-2 expression and nitric oxide synthase type II production and activity in chondrocytes through a mechanism that involves NF-κB and PI3kinase activation. In addition, ESE-1 overexpression increases IL-1-induced MMP-13 expression through NF-κB. Finally, we observed that LCN2 and NO are produced to a lesser extent in chondrocytes from ESE-1 knockout mice compared to wild type mice.

Conclusions All together, these data suggest that ESE-1 exerts clearly catabolic functions in articular cartilage.

Disclosure of Interest None Declared

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