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Gamma-oryzanol alleviates osteoarthritis development by targeting Keap1-Nrf2 binding to interfere with chondrocyte ferroptosis.
Dai, Zi-Han; Zhou, Chen-Cheng; Yu, Cai-Yu; Qian, Cheng-Jie; Jin, Shu-Qing; Du, Shi-Qi; Lv, Yi-Yun; Jin, Chen; Zheng, Gang; Zhan, Yu.
Afiliación
  • Dai ZH; Department of Ultrasound, The First Affiliated Hospital of Wenzhou Medical University, 2# Fuxue Lane, Wenzhou 325000, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
  • Zhou CC; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
  • Yu CY; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
  • Qian CJ; Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China.
  • Jin SQ; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
  • Du SQ; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
  • Lv YY; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
  • Jin C; Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China. Electronic address: jinchen@wmu.edu.cn.
  • Zheng G; Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China. Electronic address: 591759031@qq.com.
  • Zhan Y; Department of Ultrasound, The First Affiliated Hospital of Wenzhou Medical University, 2# Fuxue Lane, Wenzhou 325000, Zhejiang Province, China. Electronic address: 363622295@qq.com.
Int Immunopharmacol ; 128: 111469, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38211480
ABSTRACT
Osteoarthritis (OA) is a prevalent joint disorder pathologically correlated to chondrocyte ferroptosis. Gamma-oryzanol (γ-Ory), as a first-line drug for autonomic disorders, aroused our interest because of its antioxidant, lipid-lowering, and hypoglycemic potential. The purpose of this study was to investigate the potential impact and mechanism of γ-Ory in treating OA. And the inhibition of γ-Ory in extracellular matrix molecule (ECM) degradation, ferroptosis, and Keap1-Nrf2 binding in IL-1ß-exposed chondrocytes was detected via immunoblotting, immunofluorescence, and co-immunoprecipitation. Micro-CT, SO staining, and immunofluorescence have been conducted to assess the impact of γ-Ory treatment on ACLT-mediated OA in rats at both imaging and histological stages. We found that γ-Ory dose-dependently suppressed IL-1ß-induced ECM deterioration and chondrocyte ferroptosis. Our animal experiments revealed that γ-Ory delayed ACLT-mediated OA development. Mechanistically, γ-Ory interfered with the binding of Keap1 to Nrf2 to promote the latter's nuclear import, thereby increasing the expression of detoxification enzymes. Summarily, our works support γ-Ory's potential as a candidate drug for the treatment of OA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Fenilpropionatos / Ferroptosis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Fenilpropionatos / Ferroptosis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos