Abstract:
:The purpose of this study was to elucidate the role of the circadian gene Bmal1 in human cartilage and its crosstalk with the MAPK/ERK signaling pathway in temporomandibular joint osteoarthritis (TMJ-OA). We verified the periodical variation of the circadian gene Bmal1 and then established a modified multiple platform method (MMPM) to induce circadian rhythm disturbance leading to TMJ-OA. IL-6, p-ERK, and Bmal1 mRNA and protein expression levels were assessed by real-time RT-PCR and immunohistochemistry. Chondrocytes were treated with an ERK inhibitor (U0126), siRNA and plasmid targeting Bmal1 under IL-6 simulation; then, the cells were subjected to Western blotting to analyze the relationship between Bmal1 and the MAPK/ERK pathway. We found that sleep rhythm disturbance can downregulate the circadian gene BMAL-1 and improve phosphorylated ERK (p-ERK) and IL-6 levels. Furthermore, Bmal1 siRNA transfection was sufficient to improve the p-ERK level and aggravate OA-like gene expression changes under IL-6 stimulation. Bmal1 overexpression relieved the alterations induced by IL-6, which was consistent with the effect of U0126 (an ERK inhibitor). However, we also found that BMAL1 upregulation can decrease ERK phosphorylation, whereas ERK downregulation did not change BMAL1 expression. Collectively, this study provides new insight into the regulatory mechanism that links chondrocyte BMAL1 to cartilage maintenance and repair in TMJ-OA via the MAPK/ERK pathway and suggests that circadian rhythm disruption is a risk factor for TMJ-OA.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Chen G,Zhao H,Ma S,Chen L,Wu G,Zhu Y,Zhu J,Ma C,Zhao Hdoi
10.3389/fphar.2020.527744subject
Has Abstractpub_date
2020-09-18 00:00:00pages
527744issn
1663-9812journal_volume
11pub_type
杂志文章abstract::The cardiac action potential is critical to the production of a synchronized heartbeat. This electrical impulse is governed by the intricate activity of cardiac ion channels, among them the cardiac voltage-gated potassium (Kv) channels KCNQ1 and hERG as well as the voltage-gated sodium (Nav) channel encoded by SCN5A. ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00550
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abstract::Clopidogrel is an essential antiplatelet drug used to prevent thrombosis complications associated with atherosclerosis. However, hepatotoxicity is a potential adverse effect related to clopidogrel therapy. Exosome-derived miRNAs may be useful for improved monitoring of drug response and hepatotoxicity risk. In the pre...
journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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doi:10.3389/fphar.2017.00526
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pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2014.00005
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00759
更新日期:2018-07-16 00:00:00
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00188
更新日期:2019-03-05 00:00:00
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.01224
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doi:10.3389/fphar.2020.01328
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journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2018.00982
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abstract::Danggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action of DSD with the as...
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更新日期:2021-01-11 00:00:00
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doi:10.3389/fphar.2018.01288
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abstract::The interaction between T cell and dendritic cells (DCs) that leads to T cell activation affects the progression of the immune response including autoimmune diseases. Antigen presentation on immune cell surface, formation of an immunological synapse (IS), and specific identification of complex by T cells including two...
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journal_title:Frontiers in pharmacology
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