The role of oxidative stress in the development of knee osteoarthritis: A comprehensive research review

Liu, Lin; Luo, Pan; Yang, Mingyi; Wang, Jiachen; Hou, Weikun; Xu, Peng

doi:10.3389/fmolb.2022.1001212

Cited by 53 publications

(39 citation statements)

References 129 publications

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“…Our findings showed a significant increase of ROS in OA sf-MSCs compared with H sf-MSCs, confirming a senescent phenotype in OA cells which could amplify the progression of OA. Although not demonstrated in sf-MSCs, our data agree with the finding of elevated levels of ROS in aged and OA cartilage, both in human and animal models [ 49 ]. Furthermore, cells from human cartilage exposed to hydrogen peroxide showed hallmarks of chondrocyte senescence, such as reduced cell proliferation and lower synthesis of GAG [ 50 , 51 ].…”

Section: Discussionsupporting

confidence: 91%

Implication of Cellular Senescence in Osteoarthritis: A Study on Equine Synovial Fluid Mesenchymal Stromal Cells

Teti

Mazzotti

Gatta

et al. 2023

IJMS

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Osteoarthritis (OA) is described as a chronic degenerative disease characterized by the loss of articular cartilage. Senescence is a natural cellular response to stressors. Beneficial in certain conditions, the accumulation of senescent cells has been implicated in the pathophysiology of many diseases associated with aging. Recently, it has been demonstrated that mesenchymal stem/stromal cells isolated from OA patients contain many senescent cells that inhibit cartilage regeneration. However, the link between cellular senescence in MSCs and OA progression is still debated. In this study, we aim to characterize and compare synovial fluid MSCs (sf-MSCs), isolated from OA joints, with healthy sf-MSCs, investigating the senescence hallmarks and how this state could affect cartilage repair. Sf-MSCs were isolated from tibiotarsal joints of healthy and diseased horses with an established diagnosis of OA with an age ranging from 8 to 14 years. Cells were cultured in vitro and characterized for cell proliferation assay, cell cycle analysis, ROS detection assay, ultrastructure analysis, and the expression of senescent markers. To evaluate the influence of senescence on chondrogenic differentiation, OA sf-MSCs were stimulated in vitro for up to 21 days with chondrogenic factors, and the expression of chondrogenic markers was compared with healthy sf-MSCs. Our findings demonstrated the presence of senescent sf-MSCs in OA joints with impaired chondrogenic differentiation abilities, which could have a potential influence on OA progression.

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Section: Discussionsupporting

confidence: 91%

Implication of Cellular Senescence in Osteoarthritis: A Study on Equine Synovial Fluid Mesenchymal Stromal Cells

Teti

Mazzotti

Gatta

et al. 2023

IJMS

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“…Among them, synovial inflammation, as an initiating factor, is tied to the pathological aggravation of OA ( Arra et al, 2020 ). Various evidences have indicated that the accumulation of ROS interacts with synovitis and worsens, which may show an important influence in the development of OA ( Liu et al, 2022 ; Sunk et al, 2022 ). Inflammatory reaction exists in synovial tissues, that is, the severity of synovitis is associated with the symptoms of OA and the progress of disease to a large extent.…”

Section: Resultsmentioning

confidence: 99%

Naturally derived injectable hydrogels with ROS-scavenging property to protect transplanted stem cell bioactivity for osteoarthritic cartilage repair

Xiang

Gong

et al. 2023

Front. Bioeng. Biotechnol.

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Intra-articular injection of adipose mesenchymal stem cells (ADSCs) is a potential alternative to the treatment of osteoarthritis (OA) and has aroused great interest of clinical researchers. However, the hostile microenvironment in the joint cavity, characterized by reactive oxygen species (ROS) accumulation and excessive inflammation, disturbs the bioactivity of the transplanted stem cells. The (-)-epigallocatechin-3-O-gallate (EGCG), a green tea catechin, has attracted the researchers’ attention owing to its powerful ROS-scavenging and antioxidant properties. In this study, to avoid rapid degradation and/or depletion of EGCG, we prepare a long-lasting injectable hydrogel by EGCG and hyaluronic acid (HA). The naturally derived hydrogels with excellent biocompatibility and durable retention time can capture the redundant ROS continuously and efficiently, thus protecting ADSCs from ROS-mediated death and bioactivity inhibition, including cell survival, proliferation and chondrogenic differentiation. Intra-articular injection of this ADSCs loaded hydrogel significantly induced synovial macrophages polarization to M2 phenotype, decreased pro-inflammatory cytokines (e.g., IL-1β, MMP-13, and TNF-α) expression, promoted cartilage matrix formation, and repaired cartilage destruction in OA. This stem cell-protected hydrogel delivery strategy showed superior efficacy than ADSCs delivering or EGCG-HA injection singly, which providing a potential alternative strategy for OA management.

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“… 11 Synovial inflammation and increased angiogenesis are associated with oxidative stress. 11 , 46 ROS and oxidative stress are elevated in patients with OA. Systemic oxidative stress induces synoviocytes and chondrocytes to produce IL-6, IL-8 and prostaglandins.…”

Section: Discussionmentioning

confidence: 98%

“…The production of cytokines and growth factors by the inflamed synovium may affect the production of degrading enzymes and cartilage loss. 46 , 47 Studies have shown that the viscosity of synovial fluid is reduced and lipid peroxidation is increased in OA patients, suggesting a greater oxidative modification of synovial fluid components by ROS associated with OA. 48 Therefore, we speculate that there is a tendency to change the antioxidant status of synovial fluid in OA patients with increased GPXs activity.…”

Section: Discussionmentioning

confidence: 99%

Biological Functions of Selenoprotein Glutathione Peroxidases (GPXs) and their Expression in Osteoarthritis

Zhao¹,

Tang²,

Zhang³

et al. 2023

JIR

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Purpose In order to further study the biological functions of glutathione peroxidases (GPXs) and their expression level in patients with osteoarthritis (OA), we fully explored the potential relationship between GPXs and OA. This will provide new ideas for basic biological studies and therapeutic strategies for OA patients. Patients and Methods In this study, bioinformatics techniques were used to explore the biological functions of five GPXs. The core genes related to the biological functions of GPXs were identified by constructing a protein-protein interaction network (PPI). In addition, we utilized microarray data in public databases to analyze the expression levels of GPXs in OA patients and healthy controls. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of GPXs in OA patients and controls to validate our bioinformatic analysis results. Results Enrichment analysis showed GPXs were mainly enriched in the glutathione metabolic pathway and participate in the biological process of oxidative stress response, and further play an antioxidant role. The PPI network indicated that superoxide dismutase 1 (SOD1), superoxide dismutase 2(SOD2) and catalase (CAT) were the core proteins of this network. GPX1 was regulated by the greatest number of miRNAs. Experiments showed that the expression of GPX1 was elevated in OA patients compared with controls. Conclusion GPXs play an important antioxidant role in oxidative stress response. The expression of GPX1 was elevated in peripheral blood mononuclear cells (PBMCs) of OA patients. The changes of GPXs in OA patients may regulate the level of oxidative stress, which may influence synovial lesions and chondrocyte apoptosis.

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The role of oxidative stress in the development of knee osteoarthritis: A comprehensive research review

Cited by 53 publications

References 129 publications

Implication of Cellular Senescence in Osteoarthritis: A Study on Equine Synovial Fluid Mesenchymal Stromal Cells

Implication of Cellular Senescence in Osteoarthritis: A Study on Equine Synovial Fluid Mesenchymal Stromal Cells

Naturally derived injectable hydrogels with ROS-scavenging property to protect transplanted stem cell bioactivity for osteoarthritic cartilage repair

Biological Functions of Selenoprotein Glutathione Peroxidases (GPXs) and their Expression in Osteoarthritis

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