The Role of Ferroptosis in the Pathogenesis of Osteoarthritis

Al-Hetty, Hussein Riyadh Abdul Kareem; Abdulameer, Sada Jasim; Alghazali, Maha Waleed; Sheri, Fatime Satar; Saleh, Marwan Mahmood; Jalil, Abduladheem Turki

doi:10.1007/s00232-023-00282-0

Cited by 17 publications

(6 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 35 Ferroptosis can be used as a target for OA treatment. 36 Glutathione peroxidase 4 (GPX4) is the main regulator of ferroptosis. Previous studies have confirmed that ferroptosis inducer erastin can promote fibroblast differentiation into myofibroblasts by increasing lipid peroxidation and inhibiting GPX4 expression.…”

Section: Discussionmentioning

confidence: 99%

Geniposidic acid alleviates osteoarthritis progression through inhibiting inflammation and chondrocytes ferroptosis

Sun,

Song,

Wang

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

Osteoarthritis is one of the common diseases that seriously affects the quality of life of middle‐aged and elderly people worldwide. Geniposidic acid (GPA) is extracted from Eucommia ulmoides that exhibits various pharmacological effects. This study investigated the function of GPA on osteoarthritis (OA) in IL‐1β‐stimulated mouse chondrocytes and mouse OA model. Mouse OA model was established by destabilization of the medial meniscus (DMM) and GPA was given intraperitoneal injection. The results demonstrated that GPA could alleviate DMM‐induced OA in mice. In vitro, IL‐1β‐induced PGE2, NO, MMP1 and MMP3 were suppressed by GPA. Furthermore, IL‐1β‐induced ferroptosis was inhibited by GPA, as confirmed by the inhibition of MDA, iron, and ROS, as well as the upregulation of GSH, GPX4, and Ferritin. In addition, GPA was found to increase the expression of Nrf2 and HO‐1. And the inhibition of GPA on IL‐1β‐induced inflammation and ferroptosis were prevented by Nrf2 inhibitor. In conclusion, GPA alleviates OA progression through inhibiting inflammation and chondrocytes ferroptosis via Nrf2 signalling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Geniposidic acid alleviates osteoarthritis progression through inhibiting inflammation and chondrocytes ferroptosis

Sun,

Song,

Wang

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Clinical observations found that iron accumulation was commonly detected in the synovial fluid, synovia, and cartilage of OA patients and was positively correlated with OA severity [ 15 , 16 ]. Ferroptotic alternations, such as iron accumulation, lipid peroxidation, and mitochondrial dysfunction are closely associated with OA progression where GPX4-mediated oxidative stress and extracellular matrix degradation serve as a core mechanism [ 16 – 18 ]. Nevertheless, how ferroptosis contributes to OA pathogenesis remains to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-related genes LPCAT3 and PGD are potential diagnostic biomarkers for osteoarthritis

Wang,

Ye,

Qin

et al. 2023

J Orthop Surg Res

View full text Add to dashboard Cite

Background Osteoarthritis (OA) is the most common chronic joint disease and how ferroptosis contributes to OA has garnered much attention recently. Bioinformatics promoted the discovery of ferroptosis-related biomarkers for OA. But since OA is a whole-joint disease, sensitive biomarkers for OA are still limited. We herein focused on subchondral bone, a joint component often-ignored by existing bioinformatic reports, to identify ferroptosis-related diagnostic biomarkers for OA. Method Microarray datasets GSE51588 and GSE55457 were downloaded from Gene Expression Omnibus database. Ferroptosis-related differential expression genes (Ferr-DEGs) between OA and normal samples were identified and their functional enrichment was analyzed. Common genes for OA diagnosis were selected from Ferr-DEGs using the combination of SVM-RFE, LASSO regression, and RandomForest machine learning algorithms. Common genes' diagnostic value was verified by receiver operating characteristic (ROC) curve and their association with immune infiltration was analyzed by CIBERSORT. Finally, candidate gene’s expression was verified in chondrocytes from OA patients and in an in vitro IL-1β-induced OA model, by RT-PCR. Results Two ferroptosis-related genes, LPCAT3 and PGD, were identified as OA diagnostic biomarkers and confirmed by ROC diagnostic test. The association of LPCAT3 and PGD with the infiltration of several types of immune cells was identified. The decreased expression of LPCAT3 and PGD was both confirmed in OA chondrocytes and IL-1β-induced OA condition. Conclusions We identified ferroptosis-related genes LPCAT3 and PGD as potential diagnostic biomarkers for OA, which may offer insight into the role of ferroptosis in OA and provides useful information for the diagnosis and treatment of OA.

show abstract

“…Furthermore, ferroptosis can enhance the upregulation of MMP13 and downregulation of collagen II, thereby exacerbating ECM degradation ( 113 ). A growing body of studies has demonstrated that ferroptosis plays a significant role in the pathogenesis of OA ( 117 , 118 ). The occurrence of other forms of cell death, such as cuproptosis, in addition to the previously discussed chondrocyte death, is also closely associated with the onset of OA ( 94 , 119 ).…”

Section: The Role Of Oxidative Stress Inflammation and Chondrocyte De...mentioning

confidence: 99%

“…It was reported that melatonin could effectively downregulate the expression of senescence-related proteins p16, p21, and p-p65, and thus counteract chondrocyte senescence and the subsequent downregulation of hyaluronic acid triggered by D-galactose through activation of the SIRT1 signaling pathway ( 192 ). Ferroptosis and pyroptosis, as novel forms of PCD, have been found implicated in the pathogenesis of OA ( 80 , 118 ). Although there is currently no research reporting the impact of melatonin on ferroptosis and pyroptosis of chondrocytes, the antioxidative properties and anti-inflammatory actions of melatonin suggest its potential role as a significant inhibitor of ferroptosis and pyroptosis in chondrocytes.…”

Section: Melatonin Targeting Oxidative Stress Inflammation and Chondr...mentioning

confidence: 99%

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis

Xiong,

Peng,

Deng

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Osteoarthritis (OA) is a highly prevalent age-related musculoskeletal disorder that typically results in chronic pain and disability. OA is a multifactorial disease, with increased oxidative stress, dysregulated inflammatory response, and impaired matrix metabolism contributing to its onset and progression. The neurohormone melatonin, primarily synthesized by the pineal gland, has emerged as a promising therapeutic agent for OA due to its potential to alleviate inflammation, oxidative stress, and chondrocyte death with minimal adverse effects. The present review provides a comprehensive summary of the current understanding regarding melatonin as a promising pharmaceutical agent for the treatment of OA, along with an exploration of various delivery systems that can be utilized for melatonin administration. These findings may provide novel therapeutic strategies and targets for inhibiting the advancement of OA.

show abstract

The Role of Ferroptosis in the Pathogenesis of Osteoarthritis

Cited by 17 publications

References 49 publications

Geniposidic acid alleviates osteoarthritis progression through inhibiting inflammation and chondrocytes ferroptosis

Geniposidic acid alleviates osteoarthritis progression through inhibiting inflammation and chondrocytes ferroptosis

Ferroptosis-related genes LPCAT3 and PGD are potential diagnostic biomarkers for osteoarthritis

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis

Contact Info

Product

Resources

About