Ketogenic Diet Ameliorates Inflammation by Inhibiting the NLRP3 Inflammasome in Osteoarthritis

Abstract Background: The nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has been reported to be involved in the pathological process of osteoarthritis (OA) inflammation. The ketogenic diet (KD), which previously demonstrated to inhibit NLRP3 inflammasome activation, was evaluated to elucidate its protective mechanism against OA in rats. Methods: Anterior cruciate ligament transaction (ACLT) together with partial medial meniscectomy was used to create an OA model of rat knee joint. After treatment with KD or standard diet (SD) for 8 weeks, the knee specimens were obtained for testing. Results: KD significantly increased the content of β-hydroxybutyrate (βOHB) in rats. Compared with the SD group, KD significantly reduced the damage caused by OA in the articular cartilage and subchondral bone. NLRP3 inflammasome and inflammatory cytokines interleukin-1 β (IL-1 β) and IL-18 were significantly increased in the SD group compared with the Sham group, while their expressions were significantly decreased in rats treated with KD. In addition, MMP13 in the KD group was significantly decreased compared with that in the SD group, while COL2 was significantly increased. Conclusions: This study confirmed that KD can protect the articular cartilage and subchondral bone in a rat OA model, and its mechanism is that KD reduces the OA inflammatory response by inhibiting the activation of NLRP3 inflammasome.