Oncostatin M and IL-6 induce pro-inflammatory gene signatures in articular chondrocytes — ASN Events
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  3. Oncostatin M and IL-6 induce pro-inflammatory gene signatures in articular chondrocytes

Oncostatin M and IL-6 induce pro-inflammatory gene signatures in articular chondrocytes (#290)

Xiao Liu 1 , Ruijie Liu 1 , Ben A Croker 2 , Kate E Lawlor 1 , Gordon K Smyth 1 , Ian P Wicks 1
  1. Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic, Australia
  2. Boston Children's Hospital, Boston, Massachusetts, United States

Aims. This study describes gene expression in chondrocytes stimulated with two gp130 family cytokines - Oncostatin M (OSM) or IL-6 in conjunction with soluble IL-6 receptor (IL-6/sIL-6R, i.e. IL-6 trans-signaling) and examines the impact of deleting Suppressor of Cytokine Signaling-3 (SOCS3) in this cell type.

Methods. Wild type (WT) and SOCS3-deficient (Socs3Δ/Δcol2) murine primary chondrocytes were stimulated in vitro with OSM or IL-6/sIL-6R, for 4 hours. Total RNA was extracted and expressed genes were identified by microarray analysis (Illumina MouseWG-6 v2.0 Expression BeadChip). Validation of microarray results was performed using Taqman probes on RNA derived from chondrocytes stimulated with OSM or IL-6/sIL-6R for 1, 2, 4 or 8 hours. Gene set testing was undertaken using ROAST (rotation gene set testing). Gene ontology was performed using DAVID v6.7.

Results. Preliminary data showed that chondrocytes rely on IL-6 trans-signaling. The gene transcription profiles between OSM and IL-6/sIL-6R were highly correlated. Using pathway analysis, OSM was found to have more profound effects on chondrocyte gene expression compared to IL-6/sIL-6R, and induced greater changes in biological processes, including “Cytokine activity”, “Metallopeptidase activity” and “Proteolysis”. Further analysis distinguished between acute-phase (e.g. Ccl7) and late-stage (e.g. Il19 and Saa1) changes in gene expression for both OSM and IL-6. In the absence of SOCS3, OSM and IL-6/sIL-6R stimulation induced an IFN-like gene signature.

Conclusion. We found similarities and differences between OSM- and IL-6/sIL-6R-induced inflammatory gene signatures in chondrocytes. SOCS3 plays an important regulatory role in this cell type, as it does in hematopoietic cells. Our results suggest OSM may be a target for therapeutic intervention in inflammatory arthritis.