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Therapeutic potential of melatonin in the intervertebral disc degeneration through inhibiting the ferroptosis of nucleus pulpous cells.
Dou, Xinyu; Ma, Yunlong; Luo, Qipeng; Song, Chunyu; Liu, Meijuan; Liu, Xiao; Jia, Donglin; Li, Shuiqing; Liu, Xiaoguang.
Afiliación
  • Dou X; Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
  • Ma Y; Beijing Key Laboratory of Spinal Disease Research, Beijing, China.
  • Luo Q; Engineering Research Center of Bone and Joint Precision Medicine, Ministry of Education, Beijing, China.
  • Song C; Pain Medical Center, Peking University Third Hospital, Beijing, China.
  • Liu M; Pain Medical Center, Peking University Third Hospital, Beijing, China.
  • Liu X; Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
  • Jia D; Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Beijing, China.
  • Li S; Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
  • Liu X; Beijing Key Laboratory of Spinal Disease Research, Beijing, China.
J Cell Mol Med ; 27(16): 2340-2353, 2023 08.
Article en En | MEDLINE | ID: mdl-37329158
Ferroptosis, a novel type of cell death mediated by the iron-dependent lipid peroxidation, contributes to the pathogenesis of the intervertebral disc degeneration (IDD). Increasing evidence demonstrated that melatonin (MLT) displayed the therapeutic potential to prevent the development of IDD. Current mechanistic study aims to explore whether the downregulation of ferroptosis contributes to the therapeutic capability of MLT in IDD. Current studies demonstrated that conditioned medium (CM) from the lipopolysaccharide (LPS)-stimulated macrophages caused a series of changes about IDD, including increased intracellular oxidative stress (increased reactive oxygen species and malondialdehyde levels, but decreased glutathione levels), upregulated expression of inflammation-associated factors (IL-1ß, COX-2 and iNOS), increased expression of key matrix catabolic molecules (MMP-13, ADAMTS4 and ADAMTS5), reduced the expression of major matrix anabolic molecules (COL2A1 and ACAN), and increased ferroptosis (downregulated GPX4 and SLC7A11 levels, but upregulated ACSL4 and LPCAT3 levels) in nucleus pulposus (NP) cells. MLT could alleviate CM-induced NP cell injury in a dose-dependent manner. Moreover, the data substantiated that intercellular iron overload was involved in CM-induced ferroptosis in NP cells, and MLT treatment alleviated intercellular iron overload and protected NP cells against ferroptosis, and those protective effects of MLT in NP cells further attenuated with erastin and enhanced with ferrostatin-1(Fer-1). This study demonstrated that CM from the LPS-stimulated RAW264.7 macrophages promoted the NP cell injury. MLT alleviated the CM-induced NP cell injury partly through inhibiting ferroptosis. The findings support the role of ferroptosis in the pathogenesis of IDD, and suggest that MLT may serve as a potential therapeutic approach for clinical treatment of IDD.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Sobrecarga de Hierro / Degeneración del Disco Intervertebral / Ferroptosis / Melatonina Límite: Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Sobrecarga de Hierro / Degeneración del Disco Intervertebral / Ferroptosis / Melatonina Límite: Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: China