... E2(PGE2) and bradykinin synthesis, since HAinhibited their synthesis in a MW-dependent manner [16].Further, HA has been shown to induce analgesia in abradykinin-induced model of joint pain in rats ... synthesis [29,41]. The production of NO, another inflammatory mediator syn-thesized by the cartilage in OA and well documented in experimental OA, is stimulated by the proinflammatorycytokines ... by their proen-zymes, or decreased activity of their inhibitors [29]. Pro-inflammatory cytokines, including IL-1, TNF-α, IL-17, and IL-18, increase synthesis of MMPs, decrease MMPenzyme inhibitors,...