Chemically modified curcumin (CMC2.24) alleviates osteoarthritis progression by restoring cartilage homeostasis and inhi
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ORIGINAL ARTICLE
Chemically modified curcumin (CMC2.24) alleviates osteoarthritis progression by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis via the NF-κB/HIF-2α axis Yan Zhou 1 & Jianghua Ming 1 & Ming Deng 1 & Yaming Li 1 & Bochun Li 2 & Jia Li 3 & Yonggang Ma 1 & Zhonghui Chen 1 & Guirong Wang 4 & Shiqing Liu 1 Received: 26 November 2019 / Revised: 31 May 2020 / Accepted: 25 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The disorders of cartilage homeostasis and chondrocyte apoptosis are major events in the pathogenesis of osteoarthritis (OA). Herein, we aim to assess the chondroprotective effect and underlying mechanisms of a novel chemically modified curcumin, CMC2.24, in modulating extracellular matrix (ECM) homeostasis and inhibiting chondrocyte apoptosis. Rats underwent the anterior cruciate ligament transection, and medial menisci resection was treated by intra-articular injection with CMC2.24. In an in vitro study, rat chondrocytes were pretreated with CMC2.24 before stimulation with sodium nitroprusside (SNP). Results from in vivo studies demonstrated that the intra-articular administration of CMC2.24 ameliorated osteoarthritic cartilage destruction by promoting collagen 2a1 production and inhibited cartilage degradation and apoptosis by suppressing hypoxia-inducible factor-2a (Hif-2α), matrix metalloproteinase-3, runt-related transcription factor 2, cleaved caspase-3, and vascular endothelial growth factor and the phosphorylation of IκBα and NF-κB p65. The in vitro results revealed that CMC2.24 exhibited a strong inhibitory effect on SNP-induced chondrocyte catabolism and apoptosis. The SNP-enhanced expression of Hif-2α, a catabolic and apoptotic factor, decreased in a dose-dependent manner after CMC2.24 treatment. CMC2.24 pretreatment effectively inhibited SNP-induced IκBα and NF-κB p65 phosphorylation in rat chondrocytes, whereas pretreatment with the NF-κB antagonist BMS-345541 significantly enhanced the effects of CMC2.24. Overall, these results demonstrated that CMC2.24 attenuates OA progression by modulating ECM homeostasis and chondrocyte apoptosis by suppressing the NF-κB/Hif-2α axis, thus providing a new perspective for therapeutic strategies in OA. Key messages • Intra-articular injection of CMC2.24 ameliorated osteoarthritic cartilage destruction. • CMC2.24 promoted cell viability and decreased SNP-induced apoptotic gene expression. • SNP-induced activation of Hif-2α is inhibited by CMC2.24. • CMC2.24 inhibits NF-κB/Hif-2α axis activation to modulate ECM homeostasis and inhibit chondrocyte apoptosis. Keywords Osteoarthritis . Chemically modified curcumin (CMC2.24) . Cartilage homeostasis . NF-κB . Hif-2α * Guirong Wang [email protected] * Shiqing Liu [email protected] 1
Department of Orthopedics, Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China
2
Department of Rehabilitation, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China
3
College of Acupuncture and Bone Inj
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