Necrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis

Chen, Yong; Zhu, Chuan‐Jun; Zhu, Faming; Dai, Bingbing; Song, Sujing; Wang, Zhiqiang; Feng, Yongzeng; Ge, Jin‐Fang; Zhou, Ren‐Peng; Chen, Feihu

doi:10.1016/j.bbrc.2018.09.031

Cited by 34 publications

(21 citation statements)

References 32 publications

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“…In order to further explore the main cause affecting of cell viability, Z-VAD-FMK [9], 3-methyladenine (3-MA) [10] , and necrostatin-1 (Nec-1) [11] were used to interfere with cell apoptosis, autophagy, and necrosis, respectively. The results (Figure 6A–C) showed that in EAE (80 μg/mL) groups, there was no significant influence on the viability of the three cells with the various added inhibitors.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Wang

Dong

Zhang

et al. 2019

Toxins

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Pterocephalus hookeri (C. B. Clarke) Höeck, recorded in the Chinese Pharmacopoeia (2015 version) as a Tibetan medicine for the treatment of various diseases, especially rheumatoid arthritis, was believed to possess a slight toxicity. However, hardly any research has been carried out about it. The present study aimed to evaluate the toxicity in vivo and in vitro. Toxicity was observed by the evaluation of mice weight loss and histopathological changes in the liver. Then, the comparison research between ethyl acetate extract (EAE) and n-butanol extract (BUE) suggested that liver toxicity was mainly induced by BUE. The mechanical study suggested that BUE-induced liver toxicity was closely associated with necrosis detected by MTT and propidium iodide (PI) staining, via releasing lactate dehydrogenase (LDH), reducing the fluidity, and increasing the permeability of the cell membrane. Western blot analysis confirmed that the necrosis occurred molecularly by the up-regulation of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3), as well as the activation of the nuclear factor-kappa-gene binding (NF-κB) signaling pathway in vivo and in vitro. This finding indicated that the liver toxicity induced by BUE from P. hookeri was mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.

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Section: Resultsmentioning

confidence: 99%

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Wang

Dong

Zhang

et al. 2019

Toxins

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“…Expression level of miR-27b-3p is decreased in RA, and overexpression of miR-27b-3p significantly reduces the expression of pro-apoptotic protein caspase 3 and increases the expression of anti-apoptotic Bcl-2 in chondrocytes [73]. b) Necroptosis pathway: Activation of necroptosis pathway molecules (receptor interacting protein (RIP) 1, RIP3 and mixed lineage kinase domain-like protein phosphorylation (p-MLKL)) are detected in adjuvant arthritis (AA) rat articular cartilage and RIP1 inhibitor necrostatin-1 (Nec-1) could reduce articular cartilage damage and necroinflammation in AA rats [74]. c) Pyroptosis pathway: Extracellular acidosis, which accompanies joint inflammation of RA, significantly increases the expression of acid-sensing ion channel 1a (ASIC1a), IL-1β, IL-18, apoptosis-associated speck-like protein (ASC), neuronal apoptosis inhibitor protein, class 2 transcription activator, of the major histocomplex, heterokaryon incompatibility and telomerase-associated protein 1 (NACHT), leucine-rich repeat (LRR) and PYRIN domain (PYD) domains-containing protein 3 (NLRP3) and caspase-1 and mediates chondrocyte pyroptosis [75,76].…”

Section: Molecular Mechanisms Underlying Chondrocytes Dysfunction In Ramentioning

confidence: 99%

Section: Molecular Mechanisms Underlying Chondrocytes Dysfunction In Ramentioning

confidence: 99%

“…Resveratrol, which interfered with lymphotoxin α induced signaling pathways, abrogated inflammatory pathway/degradative/apoptotic changes activated by lymphotoxin α in articular chondrocytes [85], reduced articular damage in the animal model of RA and displayed clinical efficacy [86,87]. Necrostatin-1, which are necroptosis pathway inhibitors, ameliorated articular chondrocyte injury in the animal model [74]. Hyaluronan-inhibited MAPK pathway activation thus suppressed fibronectin fragment-stimulated NO production and reduced IL-1β-stimulated MMP-13 in human RA chondrocytes [80,88,89].…”

Section: Inhibitors Of Chondrocyte Dysfunction In Ramentioning

confidence: 99%

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Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

Tseng

Chen

Chang

et al. 2020

IJMS

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Rheumatoid arthritis (RA) is one of the inflammatory joint diseases that display features of articular cartilage destruction. The underlying disturbance results from immune dysregulation that directly and indirectly influence chondrocyte physiology. In the last years, significant evidence inferred from studies in vitro and in the animal model offered a more holistic vision of chondrocytes in RA. Chondrocytes, despite being one of injured cells in RA, also undergo molecular alterations to actively participate in inflammation and matrix destruction in the human rheumatoid joint. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the chondrocyte signatures of RA and its potential applications for diagnosis and prognosis in RA.

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“…Caspase-independent necroptotic cell death was first analysed in chondrocytes with the pseudoachondroplasia-inked mutation of the cartilage oligomeric matrix protein gene, and so far only leptin has been identified as a factor able to protect chondrocytes from TNFα-induced necroptosis [ 23 , 24 ]. In vivo inhibition of both necroptosis and apoptosis has been shown to attenuate mechanical force-mediated cartilage thinning [ 25 , 26 , 27 ]. This study presents further evidence demonstrating necroptotic activity in articular cartilage from human PTA patients.…”

Section: Introductionmentioning

confidence: 99%

Cartilage Trauma Induces Necroptotic Chondrocyte Death and Expulsion of Cellular Contents

Stolberg-Stolberg

Sambale

Hansen

et al. 2020

IJMS

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Necroptotic cell death is characterized by an activation of RIPK3 and MLKL that leads to plasma membrane permeabilization and the release of immunostimulatory cellular contents. High levels of chondrocyte death occur following intra-articular trauma, which frequently leads to post-traumatic osteoarthritis development. The aim of this study is to assess necroptosis levels in cartilage post-trauma and to examine whether chondrocyte necroptotic mechanisms may be investigated and modified in vitro. Fractured human and murine cartilage, analysed immunohistochemically for necroptosis marker expression, demonstrated significantly higher levels of RIPK3 and phospho-MLKL than uninjured controls. Primary murine chondrocytes stimulated in vitro with the TNFα and AKT-inhibitor alongside the pan-caspase inhibitor Z-VAD-fmk exhibited a significant loss of metabolic activity and viability, accompanied by an increase in MLKL phosphorylation, which was rescued by further treatment of chondrocytes with necrostatin-1. Transmission electron microscopy demonstrated morphological features of necroptosis in chondrocytes following TNFα and Z-VAD-fmk treatment. Release of dsDNA from necroptotic chondrocytes was found to be significantly increased compared to controls. This study demonstrates that cartilage trauma leads to a high prevalence of necroptotic chondrocyte death, which can be induced and inhibited in vitro, indicating that both necroptosis and its consequential release of immunostimulatory cellular contents are potential therapeutic targets in post-traumatic arthritis treatment.

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Necrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis

Cited by 34 publications

References 32 publications

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

Cartilage Trauma Induces Necroptotic Chondrocyte Death and Expulsion of Cellular Contents

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