D‐mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF‐2α‐dependent manner

Zhou, Xueman; Zheng, Yingcheng; Sun, Weihao; Zhang, Zhenzhen; Liu, Jiaqi; Yang, Wenke; Yuan, Wenxiu; Yi, Yating; Wang, Jun; Liu, Jin

doi:10.1111/cpr.13134

Cited by 106 publications

(70 citation statements)

References 57 publications

(99 reference statements)

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“…The role of ferroptosis in musculoskeletal diseases has been well documented [ 50 ]. Ferroptosis in chondrocytes leads to progression of osteoarthritis, which can be alleviated by inhibiting chondrocyte ferroptosis [ 51 , 52 ]. Studies using nucleus pulposus cells from both human and animal models have shown that ferroptosis is involved in intervertebral disc degeneration [ 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

New Insights into the Regulatory Role of Ferroptosis in Ankylosing Spondylitis via Consensus Clustering of Ferroptosis-Related Genes and Weighted Gene Co-Expression Network Analysis

Rong

Jia

et al. 2022

Genes

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The pathogenesis of ankylosing spondylitis (AS) remains undetermined. Ferroptosis is a newly discovered form of regulated cell death involved in multiple autoimmune diseases. Currently, there are no reports on the connection between ferroptosis and AS. Methods: AS samples from the Gene Expression Omnibus were divided into two subgroups using consensus clustering of ferroptosis-related genes (FRGs). Weighted gene co-expression network analysis (WGCNA) of the intergroup differentially expressed genes (DEGs) and protein–protein interaction (PPI) analysis of the key module were used to screen out hub genes. A multifactor regulatory network was then constructed based on hub genes. Results: The 52 AS patients in dataset GSE73754 were divided into cluster 1 (n = 24) and cluster 2 (n = 28). DEGs were mainly enriched in pathways related to mitochondria, ubiquitin, and neurodegeneration. Candidate hub genes, screened by PPI and WGCNA, were intersected. Subsequently, 12 overlapping genes were identified as definitive hub genes. A multifactor interaction network with 45 nodes and 150 edges was generated, comprising the 12 hub genes and 32 non-coding RNAs. Conclusions: AS can be divided into two subtypes according to FRG expression. Ferroptosis might play a regulatory role in AS. Tailoring treatment according to the ferroptosis status of AS patients can be a promising direction.

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Section: Discussionmentioning

confidence: 99%

New Insights into the Regulatory Role of Ferroptosis in Ankylosing Spondylitis via Consensus Clustering of Ferroptosis-Related Genes and Weighted Gene Co-Expression Network Analysis

Rong

Jia

et al. 2022

Genes

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“…In addition, the Nrf2 antioxidant system and ferroptosis regulate each other under inflammatory and iron overload conditions, although the detailed mechanism is still unclear [ 120 ]. A subsequent study also found that D-mannose, a compound involved in immune regulation, exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviating OA progression ( Figure 5(c) ) [ 121 ]. Through further research, GPx4 was shown to play an important role in the relationship between osteoarthritis and ferroptosis.…”

Section: Ferroptosis In Bone-related Diseasesmentioning

confidence: 99%

“…[ 119 ] with permission from 2020 Elsevier B.V.); (c) chondrocytes 24 h postindicated treatments by MitoTracker Red staining (reproduced from ref. [ 121 ] with permission from 2021 Ovid Technologies, Inc.); (d) mitochondrial membrane rupture in OA cartilage tissues by a transmission electron microscope (reproduced from ref. [ 122 ] with permission from 2022 Elsevier B.V.); (e) three-dimensional models of mouse knee joints.…”

Section: Figurementioning

confidence: 99%

“…with permission from 2020 Elsevier B.V.); (b) immunohistochemistry staining of GPX4 (reproduced from ref [119]. with permission from 2020 Elsevier B.V.); (c) chondrocytes 24 h postindicated treatments by MitoTracker Red staining (reproduced from ref [121]. with permission from 2021 Ovid Technologies, Inc.); (d) mitochondrial membrane rupture in OA cartilage tissues by a transmission electron microscope (reproduced from ref [122].…”

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confidence: 99%

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Emerging Potential Therapeutic Targets of Ferroptosis in Skeletal Diseases

Liu

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a new programmed cell death characterized by the accumulation of lipid peroxidation mediated by iron and inflammation. Since the transcentury realization of ferroptosis as an iron-dependent modality of nonapoptotic cell death in 2012, there has been growing interest in the function of ferroptosis and its relationship to clinical diseases. Recent studies have shown that ferroptosis is associated with multiple diseases, including degenerative diseases, ischemia reperfusion injury, cardiovascular disease, and cancer. Cell death induced by ferroptosis has also been related to several skeletal diseases, such as inflammatory arthritis, osteoporosis, and osteoarthritis. Research on ferroptosis can clarify the pathogenesis of skeletal diseases and provide a novel therapeutic target for its treatment. In this review, we summarize current information about the molecular mechanism of ferroptosis and describe its emerging role and therapeutic potential in skeletal diseases.

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“…The efficacy of injection of DFO in OA mice was also demonstrated in vivo [ 73 ]. Similarly, Zhou et al [ 74 ] investigated whether D-mannose mediates chondrocyte ferroptosis during OA cartilage degeneration in vitro and in vivo . They found that D-mannose could exert a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and could alleviate OA progression.…”

Section: Ferroptosis and Bone Degenerative Disordersmentioning

confidence: 99%

The Regulatory Role of Ferroptosis in Bone Homeostasis

Xiong

Chen

Lin

et al. 2022

Stem Cells International

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Ferroptosis is an iron-dependent form of programmed cell death and an important type of biological catabolism. Through the action of divalent iron or ester oxygenase, ferroptosis can induce lipid peroxidation and cell death, regulating a variety of physiological processes. The role of ferroptosis in the modulation of bone homeostasis is a significant topic of interest. Herein, we review and discuss recent studies exploring the mechanisms and functions of ferroptosis in different bone-related cells, including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. The association between ferroptosis and disorders of bone homeostasis is also explored in this review. Overall, we aim to provide a detailed overview of ferroptosis, summarizing recent understanding on its role in regulation of bone physiology and bone disease pathogenesis.

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D‐mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF‐2α‐dependent manner

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 106 publications

References 57 publications

New Insights into the Regulatory Role of Ferroptosis in Ankylosing Spondylitis via Consensus Clustering of Ferroptosis-Related Genes and Weighted Gene Co-Expression Network Analysis

New Insights into the Regulatory Role of Ferroptosis in Ankylosing Spondylitis via Consensus Clustering of Ferroptosis-Related Genes and Weighted Gene Co-Expression Network Analysis

Emerging Potential Therapeutic Targets of Ferroptosis in Skeletal Diseases

The Regulatory Role of Ferroptosis in Bone Homeostasis

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