HMGB1 and osteoarthritis: These downregulated pathways included those related to interferon signaling, inflammatory diseases such as osteoarthritis and diabetes mellitus, pattern recognition receptor signaling pathways of the innate immune system, pro-inflammatory pathways including NFκB, iNOS, neuroinflammation, TREM1, the acute phase response, HMGB1, STAT3, IL-6, TNFR, IL-1 and pathways involved in the production of ROS and RNS (Fig. 6).