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Icariin protects vertebral endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 pathway
journal contribution
posted on 2023-07-20, 05:51 authored by Yuandong Shao, Lei Sun, Guihe Yang, Wenchao Wang, Xiaoyang Liu, Ting Du, Feifei ChenFeifei Chen, Xingzhi Jing, Xingang CuiCartilage endplate (CEP) plays important roles in the onset and progression of intervertebral disc degeneration (IVDD). Icariin (ICA) is the major active ingredient of Herba Epimedii and has various biological activities such as anti-inflammatory and antioxidant, which is used to treat many degenerative diseases. However, the effects and mechanism of ICA on endplate chondrocytes are still unclear. Herein, we studied the effects of ICA on CEP degeneration and elucidated the underlying mechanisms. Endplate chondrocytes were isolated, and TNF-α and TBHP were applied to mimic an IVDD pathological environment. Also, an IVDD mice model was established by transection of bilateral facet joints to investigate the protective effect of ICA in vivo. We found that ICA treatment inhibited the chondrocytes apoptosis and the decrease of extracellular matrix production in a dose-dependent manner. Our in vivo experiments demonstrated that ICA could ameliorate IVDD development and CEP calcification. We also found that the ICA-activated Nrf-2/HO-1 pathway thus promoted the Parkin-mediated mitophagy process and inhibited chondrocytes ferroptosis, thus alleviated redox imbalance and mitochondrial dysfunction and eventually improved cell survival. Knockdown of Nrf-2 using siRNA reversed the protective effect of ICA on endplate chondrocytes apoptosis and degeneration. In conclusion, our study demonstrated that ICA could protect against CEP degeneration and calcification under IVDD pathological conditions, the associated mechanism may be related to Nrf-2/HO-1-mediated mitophagy activation and ferroptosis inhibition. Our results suggest that ICA may be a potential effective medicine for IVDD prevention and treatment.
History
Journal
FRONTIERS IN PHARMACOLOGYVolume
13Article number
ARTN 937502Location
SwitzerlandPublisher DOI
ISSN
1663-9812eISSN
1663-9812Language
EnglishPublication classification
C1.1 Refereed article in a scholarly journalPublisher
FRONTIERS MEDIA SAUsage metrics
Keywords
Science & TechnologyLife Sciences & BiomedicinePharmacology & Pharmacycartilage endplateintervertebral disc degenerationicariinNrf-2/HO-1mitophagyferroptosisINTERVERTEBRAL DISC DEGENERATIONOSTEOPOROSISFERROPTOSISPROGRESSIONBIOLOGYALPHA3214 Pharmacology and Pharmaceutical Sciences32 Biomedical and Clinical SciencesPreventionNeurodegenerative2.1 Biological and endogenous factors2 Aetiology3214 Pharmacology and pharmaceutical sciencesPharmacology and Pharmaceutical Sciences not elsewhere classified