Maresin-1 suppresses IL-1β-induced MMP-13 secretion by activating the PI3K/AKT pathway and inhibiting the NF-κB pathway in synovioblasts of an osteoarthritis rat model with treadmill exercise

Aim: Maresin-1 is a metabolite of docosahexaenoic acid (DHA) that has potential anti-inflammatory effects. To explore whether maresin-1 changes and has a therapeutic effect in osteoarthritis (OA) model rats undergoing treadmill exercise, we examined endogenous maresin-1 in a single-session treadmill experiment and OA model rats were treated with maresin-1, moreover, we examined the effects of maresin-1 on IL-1β induced rat fibroblast-like synoviocytes (FLSs) and possible mechanisms.Methods: In single-session treadmill experiment, 48 rats were randomly divided into 3 groups and performed three different intensities of exercise (15.2 m/min, 0°; 19.3 m/min, 5°; 26.8 m/min, 10°) for 60 min. Intra-articular lavage fluid (IALF) samples were harvested after 0, 2, and 4 h from each group (n = 4) and maresin-1 levels were evaluated by ELISA. Another 30 rats were treated with monosodium iodoacetate (MIA) to induce osteoarthritis and exogenous maresin-1 (MaR-1) and were divided into three groups (n = 10, OA: MIA, OAM: MIA+MaR1, and CG: control group). The level of injury was evaluated by OARSI and Mankin scores, and the levels of type II collagen and MMP13 were evaluated by immunohistochemistry. FLSs were obtained from the knee joint of SD rats, and the expression of MMP13 and activation of the PI3k/Akt and NF-κB p65 pathways in IL-1β-induced FLSs were evaluated by western blotting.Results: Maresin-1 levels were increased in IALF at 4 h after exercise, and type II collagen increased in cartilage and MMP13 decreased in the synovium after treatment with maresin-1 in MIA-induced osteoarthritis. The results of vitro experiment showed decreased MMP13, activation of the PI3k/Akt pathway, and suppression of the NF-κB p65 pathway upon treatment with maresin-1 in IL-1β-induced FLSs.Conclusions: The changes in maresin-1 in IALF, as seen in our single-section treadmill exercise, provides an explanation for the therapeutic effect of appropriate-strength treadmill exercise on osteoarthritis, and our experiments confirmed the therapeutic effect of maresin-1 both in vivo and in vitro.