Glycosaminoglycans in osteoarthritis cartilage promote inflammation by preferential activation of the lipoxygenase rather than the cyclooxygenase pathway

To determine whether glycosaminoglycans (GAG) of cartilage with osteoarthritis promote inflammation through activation of cyclooxygenase (COX)-2 and/or 5-lipoxygenase (ALOX5) pathways. GAG (50 µg/25µL) extracted from the cartilage of 30 patients subjected to total joint arthroplasty secondary to osteoarthritis (OA) or fracture or saline were injected intra-articularly (i.art.) into wild-type or ALOX5−/− SV129 mice; cell counts as well as COX2 and ALOX5 gene expression were assessed in joint washes after 6 h. GAG injection promoted acute cell migration, with predominance (> 85%) of mononuclear cells with GAG from women having greater activity than men. GAG injection significantly increased ALOX5 but not COX2 gene expression in cells of the joint washes, as compared to control. Injection of GAG from patients that sustained a fracture did not alter cell influx in ALOX5-/- mice but cell counts were significantly lower following injection of GAG from OA patients (P = 0.0016). GAG promote inflammatory cell migration into joints through triggering of the 5-lipoxygenase pathway. Sex issues may be linked to an increased inflammatory potential of GAG from female OA patients.