Mechanical stress protects against chondrocyte pyroptosis through lipoxin A4 via synovial macrophage M2 subtype polarization in an osteoarthritis model

Shen, Peng; Jia, Shuangshuo; Wang, Yan; Zhou, Xiaobin; Zhang, De‐Long; Jin, Zhuangzhuang; Wang, Ziyuan; Liu, Donghao; Bai, Lan; Yang, Yue

doi:10.1016/j.biopha.2022.113361

Cited by 18 publications

(14 citation statements)

References 56 publications

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“…There is also evidence showing that MPA produces a hypoxic environment in blood vessels, which promotes platelet aggregation, lipoxygenase activation, and LXA4 generation. In the above study, LXA4 has also been proven to promote M2 polarization and reduce inflammatory cytokines in the synovium, thereby relieving OA 148 . In summary, MPA could facilitate M2 polarization of synovial macrophages, which is a potential therapeutic tool for OA.…”

Section: Application Of Macrophage Polarization In the Treatment Of O...mentioning

confidence: 77%

Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Yuan,

Jiang,

Yang

et al. 2024

Orthopaedic Surgery

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Osteoarthritis (OA) is the most common chronic degenerative joint disease in middle‐aged and elderly people, characterized by joint pain and dysfunction. Macrophages are key players in OA pathology, and their activation state has been studied extensively. Various studies have suggested that macrophages might respond to stimuli in their microenvironment by changing their phenotypes to pro‐inflammatory or anti‐inflammatory phenotypes, which is called macrophage polarization. Macrophages accumulate and become polarized (M1 or M2) in many tissues, such as synovium, adipose tissue, bone marrow, and bone mesenchymal tissues in joints, while resident macrophages as well as other stromal cells, including fibroblasts, chondrocytes, and osteoblasts, form the joint and function as an integrated unit. In this study, we focus exclusively on synovial macrophages, adipose tissue macrophages, and osteoclasts, to investigate their roles in the development of OA. We review recent key findings related to macrophage polarization and OA, including pathogenesis, molecular pathways, and therapeutics. We summarize several signaling pathways in macrophage reprogramming related to OA, including NF‐κB, MAPK, TGF‐β, JAK/STAT, PI3K/Akt/mTOR, and NLRP3. Of note, despite the increasing availability of treatments for osteoarthritis, like intra‐articular injections, surgery, and cellular therapy, the demand for more effective clinical therapies has remained steady. Therefore, we also describe the current prospective therapeutic methods that deem macrophage polarization to be a therapeutic target, including physical stimulus, chemical compounds, and biological molecules, to enhance cartilage repair and alleviate the progression of OA.

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Section: Application Of Macrophage Polarization In the Treatment Of O...mentioning

confidence: 77%

Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Yuan,

Jiang,

Yang

et al. 2024

Orthopaedic Surgery

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“…The synovium has nerve tissue that makes it sensitive to mechanical stimulation and can precisely localize pain ( 42 ). Increased endothelial cells and monocytes protect the synovium with proper blood supply and immune response during the early stages of OA ( 43 ). Synovial fibroblasts greatly reduce as OA progresses and can be decompensated by matrix fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of cuproptosis-related genes in synovitis during osteoarthritis progress

Chang

Hu²,

Chen³

et al. 2023

Front. Immunol.

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Osteoarthritis (OA) is one of the most common refractory degenerative joint diseases worldwide. Synovitis is believed to drive joint cartilage destruction during OA pathogenesis. Cuproptosis is a novel form of copper-induced cell death. However, few studies have examined the correlations between cuproptosis-related genes (CRGs), immune infiltration, and synovitis. Therefore, we analyzed CRGs in synovitis during OA. Microarray datasets (GSE55235, GSE55457, GSE12021, GSE82107 and GSE176308) were downloaded from the Gene Expression Omnibus database. Next, we conducted differential and subtype analyses of CRGs across synovitis. Immune infiltration and correlation analyses were performed to explore the association between CRGs and immune cell abundance in synovitis. Finally, single-cell RNA-seq profiling was performed using the GSE176308 dataset to investigate the expression of CRGs in the various cell clusters. We found that the expression of five CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) was significantly increased in the OA synovium. Moreover, abundant and various types of immune cells infiltrated the synovium during OA, which was correlated with the expression of CRGs. Additionally, single-cell RNA-seq profiling revealed that the cellular composition of the synovium was complex and that their proportions varied greatly as OA progressed. The expression of CRGs differed across various cell types in the OA synovium. The current study predicted that cuproptosis may be involved in the pathogenesis of synovitis. The five screened CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) could be explored as candidate biomarkers or therapeutic targets for OA synovitis.

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“…This activation leads to downstream activation of the NF-κB signaling pathway and promotes the transcription of NLRP3 and other inflammatory factors. 37 Furthermore, exposure to these toxic particles or gases can cause extensive cell death in the lung, which releases a variety of endogenous danger molecules, such as high mobility group protein B1. These molecules further promote the activation of TLRs and downstream NLRP3.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells

cao¹,

Xu²,

Gong³

et al. 2023

COPD

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Background Macrophages are known to play a crucial role in the chronic inflammation associated with Chronic Obstructive Pulmonary Disease (COPD). BML-111, acting as a lipoxin A4 (LXA4) receptor agonist, has shown to be effective in protecting against COPD. However, the precise mechanism by which BML-111 exerts its protective effect remains unclear. Methods In order to establish a cell model of inflammation, cigarette smoke extract (CSE) was used on the RAW264.7 cell line. Afterwards, an Enzyme-linked immunosorbent assay (ELISA) kit was employed to measure concentrations of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), interleukin-18 (IL-18), and interleukin-10 (IL-10) in the cell supernatants of the RAW264.7 cells.In this study, we examined the markers of macrophage polarization using two methods: quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Additionally, we detected the expression of Notch-1 and Hes-1 through Western blotting. Results BML-111 effectively suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18, as well as inflammasome factors NLRP3 and Caspase-1, while simultaneously up-regulating the expression of the anti-inflammatory cytokine IL-10 induced by CSE. Moreover, BML-111 reduced the expression of iNOS, which is associated with M1 macrophage polarization, and increased the expression of Arg-1, which is associated with M2 phenotype. Additionally, BML-111 downregulated the expression of Hes-1 and the ratio of activated Notch-1 to Notch-1 induced by CSE. The effect of BML-111 on inflammation and macrophage polarization was reversed upon administration of the Notch-1 signaling pathway agonist Jagged1. Conclusion BML-111 has the potential to suppress inflammation and modulate M1/M2 macrophage polarization in RAW264.7 cells. The underlying mechanism may involve the Notch-1 signaling pathway.

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Mechanical stress protects against chondrocyte pyroptosis through lipoxin A4 via synovial macrophage M2 subtype polarization in an osteoarthritis model

Cited by 18 publications

References 56 publications

Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Development and validation of cuproptosis-related genes in synovitis during osteoarthritis progress

Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells

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