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Oxidative Medicine and Cellular Longevity

Oxidative Medicine and Cellular Longevity

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MCC950, the NLRP3 Inhibitor, Protects against Cartilage Degradation in a Mouse Model of Osteoarthritis

Published:3 November 2021 DOI: 10.1155/2021/4139048 PMID: 34777685
Bowei Ni, Wenbin Pei, Yunkun Qu, Rui Zhang, Xiangyu Chu, Yingguang Wang, Xiaojian Huang, Hongbo You

Abstract

Osteoarthritis (OA), characterized by chronic systemic low-level inflammation and cartilage degeneration, is a type of arthritis closely associated with aging. Inflammation and aging play a pivotal role in the occurrence and progression of OA. NLRP3 inflammasome is involved in many inflammatory and aging diseases, and NLRP3 inhibitor MCC950 has anti-inflammatory and antisenescence effects on some diseases such as Alzheimer's disease. In the present study, we found that NLRP3 protein was upregulated in human and mouse OA cartilage. Moreover, NLRP3 and Caspase1 expression induced by IL-1β in chondrocytes was blocked by MCC950. In addition, MCC950 inhibited the expression of inflammatory mediators, matrix-degrading enzymes, senescence marker protein P16 (INK4A), and β-galactosidase, as well as excessive production of ROS. Meanwhile, MCC950 promoted autophagy-related protein expression and autophagy flux under the inflammatory condition. However, autophagy inhibitor 3-MA reversed anti-inflammatory and anticatabolic effects of MCC950. In in vivo experiments, intra-articular administration of MCC950 further showed its protective effect on cartilage degeneration. Bioinformatic analysis and in vitro experimental results revealed that MCC950 might play a protective role in cartilage by regulating Nrf2/HO-1/NQO1, PI3k/Akt/mTOR, P38/MAPK, and JNK/MAPK pathways. In conclusion, our work demonstrated that NLRP3 inhibitor MCC950 might serve as a promising strategy for OA treatment.

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Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
MCC950 210826-40-7 C20H24N2O5S 138 suppliers $44.00-$1641.00
MCC950 210826-40-7 C20H24N2O5S 138 suppliers $44.00-$1641.00
MCC950 210826-40-7 C20H24N2O5S 138 suppliers $44.00-$1641.00
MCC950 210826-40-7 C20H24N2O5S 138 suppliers $44.00-$1641.00

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