Inflammatory Signaling in Cartilage: MAPK and NF-κ B Pathways in Chondrocytes and the Use of Inhibitors for Research into Pathogenesis and Therapy of Osteoarthritis

Jeremy Saklatvala

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Inflammatory Signaling in Cartilage: MAPK and NF-κ B Pathways in Chondrocytes and the Use of Inhibitors for Research into Pathogenesis and Therapy of Osteoarthritis

机译：软骨中的炎症信号：软骨细胞中的MAPK和NF-κB途径以及抑制剂在骨关节炎的发病机理和治疗研究中的应用

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Osteoarthritis is characterised by degeneration of articular cartilage. It is thought to be primarily a disease of cartilage. Inflammatory response genes, such as proteinases, cyclooxygenase, and cytokines are implicated in its pathogenesis. The evidence for expression of these genes in articular cartilage in osteoarthritis is reviewed. The expression of inflammatory response genes is controlled by four major intracellular signalling pathways. These lead to activation of the three mitogen-activated protein kinases (MAPK) and the transcriptional regulator nuclear factor kappa (NFκ )-B. The current state of knowledge of the structure of these pathways is summarized. Pharmacological inhibitors of the protein kinases of the pathways in current use are described, and insights into chondrocyte gene expression obtained with them are discussed. Very limited use of these inhibitors has yet been made in animal models of osteoarthritis.nnThe main use of the inhibitors in the near future will be in investigation of pathogenetic mechanisms in osteoarthritis, both in experimental animals and in vitro, with a view to identifying therapeutic targets. Prospects for using signalling pathway inhibitors for therapy in osteoarthritis are distant.

机译：骨关节炎的特征是关节软骨变性。人们认为它主要是软骨疾病。炎症反应基因，例如蛋白酶，环氧合酶和细胞因子与它的发病机理有关。综述了这些基因在骨关节炎的关节软骨中表达的证据。炎症反应基因的表达受四个主要的细胞内信号通路控制。这些导致三种促有丝分裂原活化的蛋白激酶（MAPK）和转录调节子核因子κ（NFκB）-B的激活。总结了这些途径的结构的当前知识状态。描述了目前使用的途径中蛋白激酶的药理抑制剂，并讨论了用它们获得的软骨细胞基因表达的见解。在骨关节炎的动物模型中，这些抑制剂的使用还非常有限。nn在不久的将来，抑制剂的主要用途将是研究实验动物和体外的骨关节炎的致病机理，以鉴定治疗方法。目标。在骨关节炎中使用信号通路抑制剂进行治疗的前景很遥远。

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《Current Drug Targets》 |2007年第2期|p.305-313|共9页
作者
Jeremy Saklatvala;
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Kennedy Institute of Rheumatology,Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH.;

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Chondrocyte, MAP kinase, NF-κ B, matrix metalloproteinase, protein kinase, protein kinase inhibitor, inflammatory response, osteoarthritis;

机译：软骨细胞;MAP激酶;NF-κB;基质金属蛋白酶;蛋白激酶;蛋白激酶抑制剂;炎症反应;骨关节炎;

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1. Inflammatory signaling in cartilage: MAPK and NF-kappaB pathways in chondrocytes and the use of inhibitors for research into pathogenesis and therapy of osteoarthritis. [J] . Saklatvala J Current drug targets-The International journal for timely in-depth reviews on drug targets . 2007,第2期

机译：软骨中的炎性信号传导：软骨细胞中的MAPK和NF-kappaB途径以及抑制剂在骨关节炎的发病机理和治疗研究中的应用。
2. Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes [J] . Sheng-long Ding, Zhi-ying Pang, Xue-mei Chen, Journal of inflammation. . 2020,第1期

机译：尿道素A衰减IL-1β诱导的炎症反应和软骨降解，通过抑制大鼠关节细胞软骨细胞中的MAPK / NF-κB信号传导途径
3. Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways [J] . Scotece M., Conde J., Abella V., Cellular Physiology and Biochemistry . 2018,第6期

机译：脂质体通过MAPKs /NF-κB途径抑制LPS激活的人类原发性骨关节炎（OA）软骨细胞的分解代谢和炎症介质。
4. cis-9, trans-11-Conjugated Linoleic Acid Exerts an Anti-inflammatory Effect in Bovine Mammary Epithelial Cells after Escherichia coli Stimulation through NF-κB Signaling Pathway [C] . Nana Ma, Guangjun Chang, Jie Huang, The 6th International Symposium on Dairy Cow Nutrition and Milk Quality（第六届“奶牛营养与牛奶质量”国际研讨会）论文集 . -1

机译：CIS-9，通过NF-κB信号通路在大肠杆菌刺激后牛乳液上皮细胞对牛乳液上皮细胞的抗炎作用施加抗炎作用
5. Inflammation in Osteoarthritis Pathogenesis: Contribution of IKKβ/NF-κB Signaling and Interplay with Chondrocyte Hypertrophy [D] . Catheline, Sarah Elizabeth. 2019

机译：骨关节炎的炎症发病机制：IKKβ/ NF-κB信号传导和与软骨细胞肥大相互作用的贡献
6. Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes [O] . Sheng-long Ding, Zhi-ying Pang, Xue-mei Chen, 2020

机译：尿石素a通过抑制大鼠关节软骨细胞中的MAPK /NF-κB信号通路来减轻IL-1β诱导的炎症反应和软骨降解
7. LncRNA SNHG1 alleviates IL-1β-induced osteoarthritis by inhibiting miR-16-5p-mediated p38 MAPK and NF-κB signaling pathways [O] . Jinlai Lei, Yahui Fu, Yan Zhuang, 2019

机译：通过抑制miR-16-5p介导的p38 mapk和NF-κB信号传导途径来减轻IL-1β诱导的骨关节炎和NF-κB信号通路

Inflammatory Signaling in Cartilage: MAPK and NF-κ B Pathways in Chondrocytes and the Use of Inhibitors for Research into Pathogenesis and Therapy of Osteoarthritis

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