Mechanical stress protects against chondrocyte pyroptosis through TGF-β1-mediated activation of Smad2/3 and inhibition of the NF-κB signaling pathway in an osteoarthritis model

Wang, Yan; Jin, Zhuangzhuang; Jia, Shuangshuo; Shen, Peng; Yang, Yue; Huang, Ying

doi:10.1016/j.biopha.2023.114216

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…This caused the generation of mechanical stresses in the articular cartilage. Moderate mechanical stress (e.g., motion) had a protective effect on cartilage and conversely exacerbated KOA [ 32 ]. The study examined the underlying mechanism of non-weight-bearing exercise as a treatment for KOA in rats by inducing them to perform knee exercises after suspension.…”

Section: Discussionmentioning

confidence: 99%

Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway

Wang,

Zhang,

et al. 2023

J Orthop Surg Res

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Background and Aim Knee osteoarthritis (KOA) is characterized by joint wear and degeneration. Unfortunately, the medical community currently lacks effective treatment options for this disease. Suspension exercise therapy is considered an effective form of non-weight-bearing exercise for treating KOA. However, its mechanism of intervention in KOA is unclear. Therefore, this study aimed to evaluate the protective effects of non-weight-bearing exercise on rats with KOA and attempted to explore the underlying mechanisms. Methods In this study, a papain-induced KOA model was constructed, and the pathological changes in cartilage tissue were observed by hematoxylin and eosin (H&E) staining and scored according to the Mankin scoring principle. The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Reverse transcription–quantitative polymerase chain reaction and Western blotting were used to detect the expression of mRNA and proteins in the TLR4/MyD88/NF-κB signaling pathway. Results H&E staining and Mankin score data confirmed that non-weight-bearing exercise significantly improved articular cartilage degradation compared with that in the model group. Further, we observed that non-weight-bearing exercise differentially reduced serum levels of IL-1β, IL-6, and TNF-α. Mechanistically, non-weight-bearing exercise downregulated gene and protein expression of TLR4, MyD88, and NF-κB in cartilage tissue. Conclusion Non-weight-bearing exercise resulted in the progression of KOA by modulating the TLR4/MyD88/NF-κB signaling pathway and decreasing the levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α to slow down the degeneration of articular cartilage.

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Section: Discussionmentioning

confidence: 99%

Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway

Wang,

Zhang,

et al. 2023

J Orthop Surg Res

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“… 86 However, inappropriate mechanical stress can harm chondrocytes and activate the NF-κB pathway, leading to increased oxidative stress, pyroptosis, and ECM degradation during OA development. 85 Moreover, in rat chondrocytes treated with H 2 O 2 , the expression of USP7, ROS, NLRP3, GSDMD-NT, active caspase-1, procaspase-1, MMP1, and MMP13 increased. Silencing, inhibition, or overexpression of the ubiquitin-specific protease 7 (USP7) gene accordingly affected the expression of those factors, whereas NLRP1, NLRP6, NLR-family CARD-containing protein 4 (NLRC4), AIM2, and ASC remained unchanged.…”

Section: Pyroptosis and Cartilage In Oamentioning

confidence: 97%

“…83,84 The study revealed that the AMPK pathway leads to pyroptosis and contributes to OA development, though it also did not mention changes in IL-18. 85,86 The article discusses various pathways that can affect chondrocyte pyroptosis and ECM degradation. 85 Upregulating TGF-β1, activating Smad2/3, and inhibiting the NF-κB pathway may potentially reduce oxidative stress and protect chondrocytes from pyroptosis, ultimately mitigating OA development.…”

Section: Pyroptosis and Cartilage In Oamentioning

confidence: 99%

“…85,86 The article discusses various pathways that can affect chondrocyte pyroptosis and ECM degradation. 85 Upregulating TGF-β1, activating Smad2/3, and inhibiting the NF-κB pathway may potentially reduce oxidative stress and protect chondrocytes from pyroptosis, ultimately mitigating OA development. Additionally, moderate stimulation of articular cartilage may potentially suppress chondrocyte pyroptosis and protect joints in OA patients by inhibiting the https://doi.org/10.2147/JIR.S445573…”

Section: Pyroptosis and Cartilage In Oamentioning

confidence: 99%

“… 83 , 84 The study revealed that the AMPK pathway leads to pyroptosis and contributes to OA development, though it also did not mention changes in IL-18. 85 , 86 …”

Section: Pyroptosis and Cartilage In Oamentioning

confidence: 99%

See 2 more Smart Citations

Pyroptosis in Osteoarthritis: Molecular Mechanisms and Therapeutic Implications

Chen,

Zeng,

Wei

et al. 2024

JIR

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Osteoarthritis (OA) is a chronic disease that causes pain and functional impairment by affecting joint tissue. Its global impact is noteworthy, causing significant economic losses and property damage. Despite extensive research, the underlying pathogenesis of OA remain an area of ongoing investigation. It has recently been discovered that the OA progression is significantly influenced by pyroptosis. Pyroptosis is a complex process that involves three pathways culminating in the assembly of Gasdermin-D (GSDMD)-N-terminal (GSDMD-NT) into pores through aggregation on the plasma membrane. The aggregation of GSDMD-NT proteins stimulates the release of inflammatory mediators, such as Interleukin-1β (IL-1β), Interleukin-18 (IL-18), and Matrix Metallopeptidase 13 (MMP13), ultimately leading to cellular lysis. The pyroptosis process in specific cells, including synovial macrophages, fibroblast-like synoviocytes (FLS), chondrocytes, and subchondral osteoblasts, contributs factor to the development of OA. Currently, the specific cells that undergo pyroptosis first are not yet fully understood, and it remains unknown whether pyroptosis in one cell can trigger the same process in other cells. Therefore, targeting pyroptosis could potentially offer a novel treatment approach for OA patients. We present a comprehensive analysis of the molecular mechanisms and key features of pyroptosis. We also outline the current research progress on various aspects, including synovial tissue, articular cartilage, extracellular matrix (ECM), and subchondral bone, with a focus on pyroptosis. The aim is to provide theoretical references for the effective management of OA.

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Advances in understanding effects of miRNAs on apoptosis, autophagy, and pyroptosis in knee osteoarthritis

An,

Sun,

Liu

et al. 2023

Mol Genet Genomics

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Mechanical stress protects against chondrocyte pyroptosis through TGF-β1-mediated activation of Smad2/3 and inhibition of the NF-κB signaling pathway in an osteoarthritis model

Cited by 11 publications

References 27 publications

Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway

Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway

Pyroptosis in Osteoarthritis: Molecular Mechanisms and Therapeutic Implications

Advances in understanding effects of miRNAs on apoptosis, autophagy, and pyroptosis in knee osteoarthritis

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