The protective effects of Donepezil (DP) against cartilage matrix destruction induced by TNF-α

Zhang, Dawei; Zhou, Yue

doi:10.1016/j.bbrc.2014.10.046

Cited by 8 publications

(6 citation statements)

References 17 publications

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“…TNF-α is wellestablished in arthritis, and anti-TNF agents have been extensively studied for therapy of inflammatory arthritis as well as osteoarthritis [18,19]. TNF-α enhances expression of MMPs and ADAMTS [8,20,21], and these increased proteases in turn cause exaggerated degradation of cartilage matrix including cartilage oligomeric matrix protein, Col II, and Aggrecan, which promotes progression of OA [22,23]. In addition, TNF-α-mediated activation of NF-κB signaling pathway is known to play an important role in the pathogenesis of OA [24].…”

Section: Discussionmentioning

confidence: 99%

Naringin Protects Against Cartilage Destruction in Osteoarthritis Through Repression of NF-κB Signaling Pathway

Zhao

Wang

et al. 2015

Inflammation

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Naringin was previously reported as a multifunctional agent. Recently, naringin was found to play a protective role in various inflammatory conditions. However, the role of naringin in cartilage degeneration and osteoarthritis (OA) progression is still unknown. TNF-α is reported to play a detrimental role in OA. Herein, primary murine chondrocytes were isolated and cultured with stimulation of TNF-α, in the presence or absence of naringin treatment. As a result, naringin attenuated TNF-α-mediated inflammation and catabolism in chondrocyte. Besides, surgically induced OA mice models were established. Cartilage degradation and OA severity were evaluated using Safranin-O staining, immunohistochemistry, and ELISA. Moreover, levels of inflammatory cytokines and catabolic markers in OA were analyzed. Oral administration of naringin alleviated degradation of cartilage matrix and protected against OA development in the surgically induced OA models. Furthermore, the protective function of naringin in cartilage and chondrocyte was possibly due to suppression of NF-κB signaling pathway. Collectively, this study presents naringin as a potential target for the treatment of joint degenerative diseases, including OA.

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Section: Discussionmentioning

confidence: 99%

Naringin Protects Against Cartilage Destruction in Osteoarthritis Through Repression of NF-κB Signaling Pathway

Zhao

Wang

et al. 2015

Inflammation

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“…According to previous studies, the up-regulated concentrations of inflammatory factors (MMP13, IL-6, and IL-8) play promotive roles in OA. TNF-a enhances expression of MMPs and ADAMTS [Zhang and Zhou, 2014;Zhao et al, 2015], and these increased proteases in turn cause exaggerated degradation of cartilage matrix including cartilage oligomeric matrix protein, Col II, and Aggrecan, which promotes progression of OA [Chan et al, 2011;Vasheghani et al, 2015]. Recombinant IL-29 augmented the mRNA expression of IL-1b, IL-6, IL-8, and MMP-3 in OA synovial fibroblasts and increased cartilage degradation [Xu et al, 2016].…”

Section: Discussionmentioning

confidence: 99%

NEAT1/miR‐181c Regulates Osteopontin (OPN)‐Mediated Synoviocyte Proliferation in Osteoarthritis

Wang

Zhang

et al. 2017

J of Cellular Biochemistry

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Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage, resulting in significant disability. Inflammatory cytokines commonly initiate the extreme changes in the synovium and cartilage microenvironment of the OA patients, subsequently resulting in cell dysfunctions, especially synoviocyte dysfunction. We revealed that the expression of osteopontin (OPN), which has been reported to regulate expression of various inflammatory factors associating with the pathogenesis of OA including matrix metalloprotease 13 (MMP13), interlukine-6 and 8 (IL-6 and IL-8), is significantly upregulated in OA tissues. In the present study, online tools were used to screen out the candidate miRNAs of OPN. Among the candidate miRNAs, miR-181c inhibited OPN mRNA expression the most strongly. Ectopic expression of miR-181c significantly repressed synoviocyte proliferation, as well as the levels of OPN, MMP13, IL-6, and IL-8. Further, the candidate lncRNAs of miR-181c were screened out by using DianaTools; among which NEAT1 showed to inversely regulate miR-181c. By performing Luciferase assays, we revealed that NEAT1 competed with OPN for miR-181c binding. After NEAT1 knockdown, MMP13, IL-6, and IL-8 expression was reduced; the synoviocyte proliferation was repressed, as well as OPN protein levels; the suppressive effect of NETA1 knockdown on synoviocyte proliferation and the indicated factors were partially reversed by miR-181c inhibition. In OA tissues, OPN mRNA, and NEAT1 expression was upregulated, whereas miR-181c expression was downregulated, indicating that targeting NEAT1 to rescue miR-181c expression so as to inhibit OPN expression and synoviocyte proliferation might be an efficient strategy for OA treatment. J. Cell. Biochem. 118: 3775-3784, 2017. © 2017 Wiley Periodicals, Inc.

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“…It exhibits inhibitory activity against IRF1 and its target matrix metalloproteinase13 (MMP13) involved in degradation of collagen, a root cause of osteoarthritis (OA). Thus, DP presents itself as a potentially effective therapeutic in OA treatment (193). VB-201, an oxidized phospholipid small molecule has been proposed as an effective atherosclerosis treatment agent in vitro and in vivo , due to its ability to directly bind to TLR2 and simultaneously inhibit IRF1 mediated signaling (194).…”

Section: Current Irf Inhibitory Strategiesmentioning

confidence: 99%

Direct Inhibition of IRF-Dependent Transcriptional Regulatory Mechanisms Associated With Disease

et al. 2019

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Interferon regulatory factors (IRFs) are a family of homologous proteins that regulate the transcription of interferons (IFNs) and IFN-induced gene expression. As such they are important modulating proteins in the Toll-like receptor (TLR) and IFN signaling pathways, which are vital elements of the innate immune system. IRFs have a multi-domain structure, with the N-terminal part acting as a DNA binding domain (DBD) that recognizes a DNA-binding motif similar to the IFN-stimulated response element (ISRE). The C-terminal part contains the IRF-association domain (IAD), with which they can self-associate, bind to IRF family members or interact with other transcription factors. This complex formation is crucial for DNA binding and the commencing of target-gene expression. IRFs bind DNA and exert their activating potential as homo or heterodimers with other IRFs. Moreover, they can form complexes (e.g., with Signal transducers and activators of transcription, STATs) and collaborate with other co-acting transcription factors such as Nuclear factor-κB (NF-κB) and PU.1. In time, more of these IRF co-activating mechanisms have been discovered, which may play a key role in the pathogenesis of many diseases, such as acute and chronic inflammation, autoimmune diseases, and cancer. Detailed knowledge of IRFs structure and activating mechanisms predisposes IRFs as potential targets for inhibition in therapeutic strategies connected to numerous immune system-originated diseases. Until now only indirect IRF modulation has been studied in terms of antiviral response regulation and cancer treatment, using mainly antisense oligonucleotides and siRNA knockdown strategies. However, none of these approaches so far entered clinical trials. Moreover, no direct IRF-inhibitory strategies have been reported. In this review, we summarize current knowledge of the different IRF-mediated transcriptional regulatory mechanisms and how they reflect the diverse functions of IRFs in homeostasis and in TLR and IFN signaling. Moreover, we present IRFs as promising inhibitory targets and propose a novel direct IRF-modulating strategy employing a pipeline approach that combines comparative in silico docking to the IRF-DBD with in vitro validation of IRF inhibition. We hypothesize that our methodology will enable the efficient identification of IRF-specific and pan-IRF inhibitors that can be used for the treatment of IRF-dependent disorders and malignancies.

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The protective effects of Donepezil (DP) against cartilage matrix destruction induced by TNF-α

Cited by 8 publications

References 17 publications

Naringin Protects Against Cartilage Destruction in Osteoarthritis Through Repression of NF-κB Signaling Pathway

Naringin Protects Against Cartilage Destruction in Osteoarthritis Through Repression of NF-κB Signaling Pathway

NEAT1/miR‐181c Regulates Osteopontin (OPN)‐Mediated Synoviocyte Proliferation in Osteoarthritis

Direct Inhibition of IRF-Dependent Transcriptional Regulatory Mechanisms Associated With Disease

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