Other major upregulated pro-inflammatory pathways and disease signaling cascades included those related to TNF receptors, iNOS, the acute phase response, osteoarthritis, diabetes mellitus, HMGB1, TREM1, oncostatin, generation of ROS and RNS, VEGF signaling, IL-8 signaling, leucocyte extravasation signaling and major innate immune-related cascades (Fig. 3 and Supplementary Fig. S3). The gene discussed is HMGB1; the disease is diabetes mellitus.