期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 160, 期 -, 页码 552-565出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2020.08.029
关键词
Homocysteine; Nucleus pulposus; Oxidative stress; Ferroptosis; Methylation
资金
- Patients or their family
- National Natural Science Foundation of China [81871796, 81802188]
- China Postdoctoral Science Foundation [2019M652110]
- National Natural Science Foundation of Zhejiang Province [LQ19H060005]
Homocysteine (Hcy) is an amino acid involved in gene methylation. Plasma concentration of Hcy is elevated in the pathological condition hyperhomocysteinemia (HHcy), which increases the risk of disorders of the vascular, nervous and musculoskeletal systems, including chondrocyte dysfunction. The present study aimed to explore the role of Hcy in intervertebral disc degeneration (IVDD), using a range of techniques. A clinical epidemiological study showed that HHcy is an independent risk factor for human IVDD. Cell culture using rat nucleus pulposus cells showed that Hcy promotes a degenerative cell phenotype (involving increased oxidative stress and cell death by ferroptosis) which is mediated by upregulated methylation of GPX4. An in-vivo mouse 'puncture' model of IVDD showed that folic acid (which is used to treat HHcy in humans) reduced the ability of diet-induced HHcy to promote IVDD. We conclude that Hcy upregulates oxidative stress and ferroptosis in the nucleus pulposus via enhancing GPX4 methylation, and is a new contributing factor in IVDD.
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