IL-1β is a key proinflammatory cytokine in OA activated by the intracellular NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, often activated in response to various danger signals. Alternatively, toll-like receptor (TLR) signaling can induce cytokine responses from macrophages, where both IL-12 p70 and TGF-β are produced in response to TLR2/TLR4 signaling, and the elevated levels of both these cytokines have been found in OA patients. Supernatants with aggregates containing NP0 induced levels of IL-1β, IL-12 p70, and TGF-β (Figure ). Increased levels of IL-1β were noted in HYA and especially the ADA conditions, suggesting that the degradation products of HA and ACAN indeed serve as DAMPs to enhance IL-1β signaling. This increased effect was absent after COL treatment. Interestingly, we observed a dampening effect of HYA and ADA on IL-12 p70