Curcumin Prevents Osteoarthritis by Inhibiting the Activation of Inflammasome NLRP3

Abstract

Curcumin has shown protective potential on osteoarthritis. However, its effect on treatment of osteoarthritis remains elusive so far. This study aimed to determine whether curcumin could ameliorate osteoarthritis in vivo and the underline mechanisms. The mice subjected to destabilization of the medial meniscus (DMM) surgery were administered curcumin. Cartilage integrity was evaluated by immunohistological staining. Expression levels of inflammatory cytokines from mice arthrodial cartilage were detected. THP-1 cells were primed by lipopolysaccharide (LPS)/ATP to induce inflammation, followed by the addition of curcumin. The expression of proinflammatory cytokines was also detected. Moreover, the expression of pro-caspase-1, cleaved caspase-1, and NLRP3 inflammasome was examined. Administration of curcumin significantly reduced osteoarthritis disease progression in DMM model of osteoarthritis. Curcumin suppressed mRNA expression of proinflammatory mediators in arthrodial cartilage of mice subjected to surgery. In LPS- and ATP-induced THP-1 macrophage cells, curcumin significantly suppressed the expression of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) at both RNA and protein levels. Compared to vehicle-treated controls, curcumin also showed remarkably increased pro-caspase-1 and decreased cleaved caspase-1. This study provides the first evidence that curcumin exerts protection on osteoarthritis by inhibition to the release of inflammasome NLRP3, leading to the downregulation of inflammatory cytokines.

Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis

“…NLRP3 may serve as a potential biomarker for the management of OA [26]. Inhibition of NLRP3 inflammasome by curcumin or estradiol could downregulate inflammatory cytokines and prevent OA progress [27,28]. In the present study, ICA attenuated LPSinduced inflammation and pyroptosis by inhibiting NLRP3 inflammasome signaling, and the overexpression of NLRP3 reduced the protective effect of ICA.…”

4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway

“…These results indicated that 4′MR might be involved in RAGE receptor-ligand axis via inhibiting RAGE expression. Certain natural substances such as curcumin have been proven to own anti-inflammatory activity by suppressing AGE-RAGE associated vascular injury and long-term complications of diabetes [ 24 ]. Therefore, the inhibition of inflammatory processes induced by AGEs-RAGE axis was considered as a good potential intervention target for therapeutic purposes.…”

NLRP3 Inflammasome and Inflammatory Diseases

“…However, the abnormal activation of the inflammasome will lead to harmful overwhelming inflammation, which may damage the infected tissue. Persistent and abnormal NLRP3 signaling is the basis of many chronic and degenerative diseases, including Stargardt disease type 1 [82], Alzheimer's disease [83], atherosclerosis [84], atrial fibrillation [85], osteoarthritis [86], and cancer [87] ( Table 1).…”