Celastrol promotes chondrocyte autophagy by regulating mTOR expression

Dai, Siming; Fan, Jian-Kun; Zhang, Yue; Hao, Zhen-Yong; Yu, Hon‐Tsen; Zhang, Zhiyi

doi:10.1097/cm9.0000000000001552

Cited by 3 publications

(4 citation statements)

References 6 publications

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“…In the mTORC1, the highly conserved serine/threonine kinase mTOR is the central catalytic subunit of the multiprotein complex and may phosphorylate multiple autophagy proteins, which results in a blockade of autophagy-initiating kinase ULK1 and functions as a negative autophagy mediator ( 78 ). Transcriptomics data and network pharmacology analysis predicted that mTOR is the direct therapeutic target of celastrol against osteoarthritis ( 79 ), and a subsequent study validated that the promotion of chondrocyte autophagy by celastrol occurs as a result of the reduction in mTOR levels ( 39 ). In addition, numerous signaling pathways converging at mTOR involve celastrol-mediated autophagy.…”

Section: Mechanisms Underlying Autophagy Modulation By Celastrolmentioning

confidence: 97%

“…Extensive experimentation has indicated that autophagy modulation may be an important mechanism underlying the anti-tumor therapeutic effect of celastrol (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Celastrol also alleviates inflammatory reactions and restrains the immune response through autophagic pathways (31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Furthermore, autophagy has a role when celastrol exerts neuroprotective, anti-atherosclerosis, anti-pulmonary fibrosis and anti-macular degeneration effects (41)(42)(43)(44)(45)(46)(47)(48).…”

Section: Autophagy Regulation By Celastrolmentioning

confidence: 99%

“…During this process, large amounts of inflammatory cytokines, such as IL-1β, are released into the osteoarthritis cartilage, which induces chondrocyte apoptosis ( 70 ). Autophagy deficiency is always accompanied by an increase in apoptotic chondrocytes, whereas celastrol treatment resulted in obvious reversal effects ( 39 ). By restoring autophagy activation, celastrol inhibited the IL-1β-stimulated inflammatory response, counteracted chondrocyte apoptosis and achieved a promising therapeutic effect against osteoarthritis in vitro and in vivo ( 40 ).…”

Section: Autophagy Regulation By Celastrolmentioning

confidence: 99%

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Autophagy in the pharmacological activities of celastrol (Review)

Zhang

Wang

et al. 2023

Exp Ther Med

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Celastrol, a natural compound extracted from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, possesses broad-spectrum pharmacological properties. Autophagy is an evolutionarily conserved catabolic process through which cytoplasmic cargo is delivered to the lysosomes for degradation. Autophagy dysregulation contributes to multiple pathological processes. Therefore, targeting autophagic activity is a promising therapy for various diseases, as well as a drug-development strategy. According to previous studies, autophagy is specifically targeted and may be altered in response to celastrol treatment, highlighting that autophagy modulation is an important mechanism underlying the therapeutic efficacy of celastrol for the treatment of various diseases.The present study summarizes the currently available information regarding the role of autophagy in the effect of celastrol to exert anti-tumor, anti-inflammatory, immunomodulatory, neuroprotective, anti-atherosclerosis, anti-pulmonary fibrosis and anti-macular degeneration activities. The diverse signaling pathways involved are also analyzed to provide insight into the mechanisms of action of celastrol and thereby pave the way for establishing celastrol as an efficacious autophagy modulator in clinical practice. Contents 1. Introduction 2. An overview of autophagy 3. Autophagy regulation by celastrol 4. Mechanisms underlying autophagy modulation by celastrol 5. Conclusion and future perspectives

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Section: Mechanisms Underlying Autophagy Modulation By Celastrolmentioning

confidence: 97%

Section: Autophagy Regulation By Celastrolmentioning

confidence: 99%

Section: Autophagy Regulation By Celastrolmentioning

confidence: 99%

See 1 more Smart Citation

Autophagy in the pharmacological activities of celastrol (Review)

Zhang

Wang

et al. 2023

Exp Ther Med

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“…Many small molecule compounds and natural plant components play protective roles in OA by activating autophagy, such as isoimperatorin, delphinidin, celastrol, curcumin and astragaloside IV ( Liu, Meng, Jing, & Zhou, 2017 ; Ouyang, Jiang, Fang, Cui, & Cai, 2017 ; Lee et al, 2020 ; Xiao et al, 2020 ; Dai et al, 2021 ). Baicalin protects chondrocytes against the degradation of ECM through activating autophagy via miR-766-3p/AIFM1 axis ( Li, Cheng, & Liu, 2020 ).…”

Section: Drugs Targeting Autophagy For Osteoarthritis Treatmentmentioning

confidence: 99%

New insights into the interplay between autophagy and cartilage degeneration in osteoarthritis

Zhao

Dai

et al. 2022

Front. Cell Dev. Biol.

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Autophagy is an intracellular degradation system that maintains the stable state of cell energy metabolism. Some recent findings have indicated that autophagy dysfunction is an important driving factor for the occurrence and development of osteoarthritis (OA). The decrease of autophagy leads to the accumulation of damaged organelles and macromolecules in chondrocytes, which affects the survival of chondrocytes and ultimately leads to OA. An appropriate level of autophagic activation may be a new method to prevent articular cartilage degeneration in OA. This minireview discussed the mechanism of autophagy and OA, key autophagy targets regulating OA progression, and evaluated therapeutic applications of drugs targeting autophagy in preclinical and clinical research. Some critical issues worth paying attention to were also raised to guide future research efforts.

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Oxymatrine protects articular chondrocytes from IL-1β-induced damage through autophagy activation via AKT/mTOR signaling pathway inhibition

Lu,

Bian,

Wang

et al. 2024

J Orthop Surg Res

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Background Osteoarthritis (OA) is a common degenerative joint disease characterized by persistent articular cartilage degeneration and synovitis. Oxymatrine (OMT) is a quinzolazine alkaloid extracted from the traditional Chinese medicine, matrine, and possesses anti-inflammatory properties that may help regulate the pathogenesis of OA; however, its mechanism has not been elucidated. This study aimed to investigate the effects of OMT on interleukin-1β (IL-1β)-induced damage and the potential mechanisms of action. Methods Chondrocytes were isolated from Sprague-Dawley rats. Toluidine blue and Collagen II immunofluorescence staining were used to determine the purity of the chondrocytes. Thereafter, the chondrocytes were subjected to IL-1β stimulation, both in the presence and absence of OMT, or the autophagy inhibitor 3-methyladenine (3-MA). Cell viability was assessed using the MTT assay and SYTOX Green staining. Additionally, flow cytometry was used to determine cell apoptosis rate and reactive oxygen species (ROS) levels. The protein levels of AKT, mTOR, LC3, P62, matrix metalloproteinase-13, and collagen II were quantitatively analyzed using western blotting. Immunofluorescence was used to assess LC3 expression. Results OMT alleviated IL-1β-induced damage in chondrocytes, by increasing the survival rate, reducing the apoptosis rates of chondrocytes, and preventing the degradation of the cartilage matrix. In addition, OMT decreased the ROS levels and inhibited the AKT/mTOR signaling pathway while promoting autophagy in IL-1β treated chondrocytes. However, the effectiveness of OMT in improving chondrocyte viability under IL-1β treatment was limited when autophagy was inhibited by 3-MA. Conclusions OMT decreases oxidative stress and inhibits the AKT/mTOR signaling pathway to enhance autophagy, thus inhibiting IL-1β-induced damage. Therefore, OMT may be a novel and effective therapeutic agent for the clinical treatment of OA.

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Celastrol promotes chondrocyte autophagy by regulating mTOR expression

Abstract: Supplemental Digital Content is available in the text

Cited by 3 publications

References 6 publications

Autophagy in the pharmacological activities of celastrol (Review)

Autophagy in the pharmacological activities of celastrol (Review)

New insights into the interplay between autophagy and cartilage degeneration in osteoarthritis

Oxymatrine protects articular chondrocytes from IL-1β-induced damage through autophagy activation via AKT/mTOR signaling pathway inhibition

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