Spermidine protects cartilage from IL-1β-mediated ferroptosis

Cheng, Qi; Ni, Li; Liu, Ang; Huang, Xiaoxiong; Xiang, Pan; Zhang, Qin; Yang, Huilin

doi:10.1007/s11010-023-04889-8

Cited by 5 publications

(1 citation statement)

References 34 publications

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“…[27] The antioxidant spermidine can inhibit ferroptosis in chondrocytes and alleviate RA. [28] Macrophage ferroptosis induced by iron overload exacerbates the development of RA, and M1 macrophages are sensitive to ferroptosis. M1 macrophages have higher iron levels lower levels of GSH than other cells, which increases their susceptibility to ferroptosis.…”

Section: Iron Metabolism and Ramentioning

confidence: 99%

Iron metabolism and arthritis: Exploring connections and therapeutic avenues

Zhuo,

Xiao,

Tang

et al. 2024

Chinese Medical Journal

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Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

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Section: Iron Metabolism and Ramentioning

confidence: 99%

Iron metabolism and arthritis: Exploring connections and therapeutic avenues

Zhuo,

Xiao,

Tang

et al. 2024

Chinese Medical Journal

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The role of ferroptosis in osteoarthritis: Progress and prospects

Sheng,

Liao,

Wang

et al. 2024

Biochemical and Biophysical Research Communications

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Spermidine attenuates chondrocyte inflammation and cellular pyroptosis through the AhR/NF-κB axis and the NLRP3/caspase-1/GSDMD pathway

Guo,

Feng,

Yang

et al. 2024

Front. Immunol.

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IntroductionOsteoarthritis (OA) is a prevalent chronic degenerative disease, marked by a complex interplay of mechanical stress, inflammation, and metabolic imbalances. Recent studies have highlighted the potential of spermidine (SPD), a naturally occurring polyamine known for its anti-inflammatory and antioxidant properties, as a promising therapeutic agent for OA. This study delves into the therapeutic efficacy and mechanistic pathways of SPD in mitigating OA symptoms.MethodsForty Sprague-Dawley rats were randomly assigned to four groups, including the CG (sham operation), model (anterior cruciate ligament transection [ACLT], and treatment (ACLT + two different doses of SPD) groups. In vivo, correlations between OA severity and different interventions were assessed by ELISA, X-rays, CT imaging, histological staining, and immunohistochemistry. In vitro, IL-1β was used to trigger chondrocyte inflammation, and SPD’s cytotoxicity was assessed in primary rat chondrocytes. Next, inflammatory markers, extracellular matrix (ECM) proteins, and pathway marker proteins were detected in chondrocytes administered IL-1β alone, SPD, or aryl hydrocarbon receptor (AhR) silencing, by qRT-PCR, Griess reaction, ELISA, Western blot, and immunofluorescence. Morphological alterations and pyroptosis in chondrocytes were examined by transmission electron microscopy (TEM) and flow cytometry.ResultsOur research reveals that SPD exerts significant anti-inflammatory and antipyroptotic effects on IL-1β-treated chondrocytes and in anterior cruciate ligament transection (ACLT) rat models of OA, primarily through interaction with the Aryl hydrocarbon receptor (AhR). Specifically, SPD’s binding to AhR plays a crucial role in modulating the inflammatory response and cellular pyroptosis by inhibiting both the AhR/NF-κB and NLRP3/caspase-1/GSDMD signaling pathways. Furthermore, the knockdown of AhR was found to negate the beneficial effects of SPD, underscoring the centrality of the AhR pathway in SPD’s action mechanism. Additionally, SPD was observed to promote the preservation of cartilage integrity and suppress ECM degradation, further supporting its potential as an effective intervention for OA.DiscussionCollectively, our findings propose SPD as a novel therapeutic approach for OA treatment, targeting the AhR pathway to counteract the disease’s progression and highlighting the need for further clinical evaluation to fully establish its therapeutic utility.

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Spermidine protects cartilage from IL-1β-mediated ferroptosis

Cited by 5 publications

References 34 publications

Iron metabolism and arthritis: Exploring connections and therapeutic avenues

Iron metabolism and arthritis: Exploring connections and therapeutic avenues

The role of ferroptosis in osteoarthritis: Progress and prospects

Spermidine attenuates chondrocyte inflammation and cellular pyroptosis through the AhR/NF-κB axis and the NLRP3/caspase-1/GSDMD pathway

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