Ergosterol limits osteoarthritis development and progression through activation of Nrf2 signaling

Cai, Dawei; Yan, Hao; Li, Jun; Chen, Sichun; Jiang, Longhai; Wang, Xiaoxu; Qin, Jian

doi:10.3892/etm.2021.9627

Cited by 9 publications

(4 citation statements)

References 40 publications

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“…Furthermore, a recent study found that activating Nrf2 reduced nociceptive hypersensitivity by reducing mitochondrial dysfunction and neuro-inflammation in a dimethyl fumarate-induced peripheral nerve injury model [ 111 ]. These findings suggest that the Nrf2 signaling pathway may be a promising therapeutic approach for chronic pain associated with knee OA treatment [ 112 , 113 , 114 ]. In this study, we found that in OA-control rats, Nrf2 and HO-1 proteins were down-regulated, but COX-2 was up-regulated.…”

Section: Discussionmentioning

confidence: 99%

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

et al. 2022

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The most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) method and in vitro studies are conducted in fibroblast-like synoviocyte cells (FLS). The pain was assessed using weight-bearing and paw-withdrawal tests. CA supplementation significantly reduced pain. The enzyme-linked immunosorbent assay (ELISA) method was used to detect inflammatory proteins in the blood and intra-articular synovial fluid (IASF), and CA reduced the levels of inflammatory proteins. Histopathological studies were performed on knee-tissue samples using toluidine blue and hematoxylin and eosin (H and E) assays. CA treatment improved synovial protection and decreased cartilage degradation while decreasing zonal depth lesions. Furthermore, Western blotting studies revealed that the CA-treated group activated nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) and reduced the expression of cyclooxygenase-2 (COX-2). FLS cells were isolated from the knee joints and treated with IL-1β to stimulate the inflammatory response and increase reactive oxygen species (ROS). The matrix metalloproteinase protein (MMP’s) levels (MMP-3, and MMP-13) were determined using the reverse transcription-polymerase chain reaction (RT-PCR), and CA treatment reduced the MMP’s expression levels. When tested using the 2′,7′-dicholorodihydrofluroscene diacetate (DCFDA) assay and the 5,5′,6,6′-tetracholoro-1,1′,3,3′-tertraethylbenzimidazolcarboc janine iodide (JC-1) assay in augmented ROS FLS cells, CA reduced the ROS levels and improved the mitochondrial membrane permeability. This study’s investigation suggests that CA significantly alleviates knee OA both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

et al. 2022

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“…The isolated chondrocytes were first subjected to immunofluorescent staining using a type II collagen antibody to determine whether or not the chondrocytes possessed the characteristic of expressing and secreting type II collagen [ 34 ]. Further, the isolated chondrocytes were detected by flow cytometry assay to define the proportion of chondrocytes positive for type II collagen, while chondrocytes without the addition of the type II collagen antibody and SW1353 cells were used as the negative control.…”

Section: Methodsmentioning

confidence: 99%

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis

Chen

Liu

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Gubitong Recipe (GBT) is a prescription based on the Traditional Chinese Medicine (TCM) theory of tonifying the kidney yang and strengthening the bone. A previous multicentral randomized clinical trial has shown that GBT can effectively relieve joint pain and improve quality of life with a high safety in treating osteoarthritis (OA). This study is aimed at elucidating the active compounds, potential targets, and mechanisms of GBT for treating OA. Method. The network pharmacology method was used to predict the key active compounds, targets, and mechanisms of GBT in treating OA. An OA rat model was established with Hulth surgery, and the pathological changes of articular cartilage were observed to evaluate the effects of GBT. Chondrocytes were stimulated with LPS to establish in vitro models, and key targets and mechanisms predicted by network pharmacology were verified via qRT-PCR, ELISA, western blot, and immunofluorescence. The Contribution Index Model and molecular docking were used to determine the key active compounds of GBT and the major nodes affecting predicted pathways. Result. A total of 500 compounds were acquired from related databases, where 87 active compounds and their 254 corresponding targets were identified. 2979 OA-related genes were collected from three databases, 150 of which were GBT-regulating OA genes. The compound-target network weight analysis and PPI results showed that IL-6 and PGE2 are key targets of GBT in treating OA. KEGG results showed that PI3K/AKT, Toll-like receptor, NFκB, TNF, and HIF-1 are the key signaling pathways. An in vivo experiment showed that GBT could effectively suppress cartilage degradation of OA rats. In vitro experiments demonstrated that GBT can inhibit the key targets of KEGG-related pathways. Molecular-docking results suggested that luteolin, licochalcone A, and β-carotene were key targets of GBT, and the mechanisms may be associated with the NFκB signaling pathway. Blockage experiments showed that the NFκB pathway is the key pathway of GBT in treating OA. Conclusion. This study verified that GBT can effectively protect articular cartilage through multitarget and multipathway, and its inhibitory effect on the NFκB pathway is the most key mechanism in treating OA.

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“…Ergosterol ( 50 ) is isolated from the fungus Agaricus campestris . Ergosterol has shown chondroprotective activity by activating the NRF2/HO-1 signaling pathway in mouse chondrocytes ( Cai et al, 2021b ). Maltol ( 51 ), an aromatic natural metabolite isolated from red ginseng, has shown various biological effects, including anti-inflammation and anti-oxidative stress.…”

Section: The Interaction Between Oxidative Stress and Oamentioning

confidence: 99%

Natural compounds protect against the pathogenesis of osteoarthritis by mediating the NRF2/ARE signaling

Yang

Liu

et al. 2023

Front. Pharmacol.

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Osteoarthritis (OA), a chronic joint cartilage disease, is characterized by the imbalanced homeostasis between anabolism and catabolism. Oxidative stress contributes to inflammatory responses, extracellular matrix (ECM) degradation, and chondrocyte apoptosis and promotes the pathogenesis of OA. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central regulator of intracellular redox homeostasis. Activation of the NRF2/ARE signaling may effectively suppress oxidative stress, attenuate ECM degradation, and inhibit chondrocyte apoptosis. Increasing evidence suggests that the NRF2/ARE signaling has become a potential target for the therapeutic management of OA. Natural compounds, such as polyphenols and terpenoids, have been explored to protect against OA cartilage degeneration by activating the NRF2/ARE pathway. Specifically, flavonoids may function as NRF2 activators and exhibit chondroprotective activity. In conclusion, natural compounds provide rich resources to explore the therapeutic management of OA by activating NRF2/ARE signaling.

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Ergosterol limits osteoarthritis development and progression through activation of Nrf2 signaling

Cited by 9 publications

References 40 publications

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis

Natural compounds protect against the pathogenesis of osteoarthritis by mediating the NRF2/ARE signaling

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