Moracin attenuates LPS-induced inflammation in nucleus pulposus cells via Nrf2/HO-1 and NF-κB/TGF-β pathway

Gu, Ronghe; Huang, Zonggui; Liu, Huijiang; Qing, Qiwen; Zou, Zhuan; Yang, Lijing; Su, Zhongyi; Huang, Weiguo

doi:10.1042/bsr20191673

Cited by 17 publications

(8 citation statements)

References 27 publications

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“…Estrogen supplementation can enhance antioxidant capacity and correct redox imbalance stress 78 . In addition, the partial or whole functional deficiency of mitochondrial antioxidant enzymes is also critical in many other IDD processes induced by hyperosmolarity, mechanical overloading, AGE accumulation, or lipopolysaccharide 6,49,79,80 . The effects of biologically active components used to treat IDD have greatly improved in recent years.…”

Section: Mitochondrial Dysfunction and Idd Pathogenesismentioning

confidence: 99%

“…Jiao et al79 Hypertonic milieu NP cell culture Hyperosmolarity culture significantly decreased the total SOD activity compared with the in situosmolarity culture 79. Gu et al80 Lipopolysaccharides NP cell culture NP cells treated with LPS exhibited reduced SOD and catalase activity levels.80 Tang et al 81 H2O2/Honokiol NP cell culture Honokiol pretreatment significantly reversed the H2O2-suppressed expression of the SOD and Gpx1 genes.…”

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confidence: 99%

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Mitochondrial quality control in intervertebral disc degeneration

Song

Geng

et al. 2021

Exp Mol Med

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Intervertebral disc degeneration (IDD) is a common and early-onset pathogenesis in the human lifespan that can increase the risk of low back pain. More clarification of the molecular mechanisms associated with the onset and progression of IDD is likely to help establish novel preventive and therapeutic strategies. Recently, mitochondria have been increasingly recognized as participants in regulating glycolytic metabolism, which has historically been regarded as the main metabolic pathway in intervertebral discs due to their avascular properties. Indeed, mitochondrial structural and functional disruption has been observed in degenerated nucleus pulposus (NP) cells and intervertebral discs. Multilevel and well-orchestrated strategies, namely, mitochondrial quality control (MQC), are involved in the maintenance of mitochondrial integrity, mitochondrial proteostasis, the mitochondrial antioxidant system, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis. Here, we address the key evidence and current knowledge of the role of mitochondrial function in the IDD process and consider how MQC strategies contribute to the protective and detrimental properties of mitochondria in NP cell function. The relevant potential therapeutic treatments targeting MQC for IDD intervention are also summarized. Further clarification of the functional and synergistic mechanisms among MQC mechanisms may provide useful clues for use in developing novel IDD treatments.

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Section: Mitochondrial Dysfunction and Idd Pathogenesismentioning

confidence: 99%

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confidence: 99%

Mitochondrial quality control in intervertebral disc degeneration

Song

Geng

et al. 2021

Exp Mol Med

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“…Surgically-induced OA models such as DMM and ACLT are the most commonly applied method of OA induction because of the ease by which the condition can be induced [ 143 , 151 ]. Moracin, a natural flavonoid compound extracted from Cortex Mori (the root bark of Morus alba ), is known for its anti-inflammatory activity via the suppression of NF-κB signaling pathway activation [ 207 , 208 ]. Moracin inhibits IL-1β-induced catabolic gene expression in rat primary chondrocytes through the inhibition of NF-κB signaling via Nrf2/HO1 activation.…”

Section: Pharmacological Treatment For Oa Protectionmentioning

confidence: 99%

Pharmacological Targeting of Heme Oxygenase-1 in Osteoarthritis

et al. 2021

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Osteoarthritis (OA) is a common aging-associated disease that clinically manifests as joint pain, mobility limitations, and compromised quality of life. Today, OA treatment is limited to pain management and joint arthroplasty at the later stages of disease progression. OA pathogenesis is predominantly mediated by oxidative damage to joint cartilage extracellular matrix and local cells such as chondrocytes, osteoclasts, osteoblasts, and synovial fibroblasts. Under normal conditions, cells prevent the accumulation of reactive oxygen species (ROS) under oxidatively stressful conditions through their adaptive cytoprotective mechanisms. Heme oxygenase-1 (HO-1) is an iron-dependent cytoprotective enzyme that functions as the inducible form of HO. HO-1 and its metabolites carbon monoxide and biliverdin contribute towards the maintenance of redox homeostasis. HO-1 expression is primarily regulated at the transcriptional level through transcriptional factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), specificity protein 1 (Sp1), transcriptional repressor BTB-and-CNC homology 1 (Bach1), and epigenetic regulation. Several studies report that HO-1 expression can be regulated using various antioxidative factors and chemical compounds, suggesting therapeutic implications in OA pathogenesis as well as in the wider context of joint disease. Here, we review the protective role of HO-1 in OA with a focus on the regulatory mechanisms that mediate HO-1 activity.

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“…Nrf2 can reduce the production of ROS from the source by maintaining mitochondrial homeostasis, thereby maintaining the redox balance in NP cells (Tang et al, 2019;Wang K. et al, 2019). Various drugs can inhibit IDD by activating the Nrf2 signaling pathway (Gu et al, 2019;Song et al, 2021;Wang K. et al, 2019;Wang et al, 2020a;Zhong et al, 2021). In this study, we confirmed that BARD increased the expression and nuclear translocation of Nrf2 and downstream HO-1 expression also significantly increased.…”

Section: Discussionmentioning

confidence: 99%

Bardoxolone Methyl Ameliorates Compression-Induced Oxidative Stress Damage of Nucleus Pulposus Cells and Intervertebral Disc Degeneration Ex Vivo

Tian

Duan

Yang

et al. 2022

Front. Bioeng. Biotechnol.

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Intervertebral disc degeneration (IDD) is the main cause of low back pain, and little is known about its molecular and pathological mechanisms. According to reports, excessive compression is a high-risk factor for IDD; compressive stress can induce oxidative stress in nucleus pulposus (NP) cells during IDD progression that, in turn, promotes cell apoptosis and extracellular matrix (ECM) degradation. Currently, NP tissue engineering is considered a potential method for IDD treatment. However, after transplantation, NP cells may experience oxidative stress and induce apoptosis and ECM degradation due to compressive stress. Therefore, the development of strategies to protect NP cells under excessive compressive stress, including pretreatment of NP cells with antioxidants, has important clinical significance. Among the various antioxidants, bardoxolone methyl (BARD) is used to protect NP cells from damage caused by compressive stress. Our results showed that BARD can protect the viability of NP cells under compression. BARD inhibits compression-induced oxidative stress in NP cells by reducing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde. Thus, BARD has a protective effect on the compression-induced apoptosis of NP cells. This is also supported by changes in the expression levels of proteins related to the mitochondrial apoptosis pathway. In addition, BARD can inhibit ECM catabolism and promote ECM anabolism in NP cells. Finally, the experimental results of the mechanism show that the activation of the Nrf2 signaling pathway participates in the protection induced by BARD in compressed NP cells. Therefore, to improve the viability and biological functions of NP cells under compression, BARD should be used during transplantation.

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Moracin attenuates LPS-induced inflammation in nucleus pulposus cells via Nrf2/HO-1 and NF-κB/TGF-β pathway

Cited by 17 publications

References 27 publications

Mitochondrial quality control in intervertebral disc degeneration

Mitochondrial quality control in intervertebral disc degeneration

Pharmacological Targeting of Heme Oxygenase-1 in Osteoarthritis

Bardoxolone Methyl Ameliorates Compression-Induced Oxidative Stress Damage of Nucleus Pulposus Cells and Intervertebral Disc Degeneration Ex Vivo

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