Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway.
Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway.
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昼夜节律蛋白 Bmal1 通过 MAPK/ERK 通路调节颞下颌关节骨关节炎的软骨基因表达
DOI：
10.3389/fphar.2020.527744
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发表时间：
2020
影响因子：
5.6
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Chen G;Zhao H;Ma S;Chen L;Wu G;Zhu Y;Zhu J;Ma C;Zhao H
本研究的目的是阐明昼夜节律基因Bmal 1在人软骨中的作用及其与MAPK/ERK信号通路在颞下颌关节骨关节炎（TMJ-OA）中的相互作用。我们验证了昼夜节律基因Bmal 1的周期性变化，并建立了一个改进的多平台方法（MMPM），诱导昼夜节律紊乱导致TMJ-OA。采用实时荧光定量RT-PCR和免疫组织化学方法检测IL-6、p-ERK和Bmal 1 mRNA和蛋白表达水平。在IL-6刺激下，分别用ERK抑制剂U 0126、siRNA和靶向Bmal 1的质粒处理软骨细胞，通过Western blotting分析Bmal 1与MAPK/ERK通路的关系。我们发现，睡眠节律紊乱可下调昼夜节律基因BMAL-1，提高磷酸化ERK（p-ERK）和IL-6水平。Bmal 1 siRNA转染可显著提高IL-6刺激下的p-ERK水平，加重OA样基因表达的变化。Bmal 1过表达可减轻IL-6诱导的细胞凋亡，这与ERK抑制剂U 0126的作用一致。然而，我们也发现BMAL 1上调可以降低ERK磷酸化，而ERK下调并不改变BMAL 1的表达。总的来说，这项研究提供了新的见解，通过MAPK/ERK途径将软骨细胞BMAL 1与TMJ-OA中的软骨维护和修复联系起来的调节机制，并表明昼夜节律破坏是TMJ-OA的危险因素。
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.
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影响因子：
--
作者：
Song C;Wang J;Kim B;Lu C;Zhang Z;Liu H;Kang H;Sun Y;Guan H;Fang Z;Li F
通讯作者：
Li F
影响因子：
3.7
作者：
Kouri VP;Olkkonen J;Kaivosoja E;Ainola M;Juhila J;Hovatta I;Konttinen YT;Mandelin J
通讯作者：
Mandelin J
影响因子：
13.9
作者：
Mohawk JA;Green CB;Takahashi JS
通讯作者：
Takahashi JS
分解代谢细胞因子通过 NFкB 依赖性途径破坏生物钟和软骨中时钟控制基因的表达
影响因子：
7
作者：
Guo B;Yang N;Borysiewicz E;Dudek M;Williams JL;Li J;Maywood ES;Adamson A;Hastings MH;Bateman JF;White MR;Boot-Handford RP;Meng QJ
通讯作者：
Meng QJ
影响因子：
5.6
作者：
Kc, Ranjan;Li, Xin;Voigt, Robin M.;Ellman, Michael B.;Summa, Keith C.;Vitaterna, Martha Hotz;Keshavarizian, Ali;Turek, Fred W.;Meng, Qing-Jun;Stein, Gary S.;van Wijnen, Andre J.;Chen, Di;Forsyth, Christopher B.;Im, Hee-Jeong
通讯作者：
Im, Hee-Jeong