Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis.
Humans; *Apoptosis; *Apoptosis; *ERK1/2; *Nrf2; *Osteoarthritis; *Redox; Oxidative Stress; Osteoarthritis/*metabolism; NF-E2-Related Factor 2/genetics/*metabolism; Up-Regulation; MAP Kinase Signaling System; Chondrocytes/*physiology; Caspases/metabolism; Cells; Cultured; 70-kDa/metabolism; Ribosomal Protein S6 Kinases; Carboxylic Ester Hydrolases/metabolism; ets-Domain Protein Elk-1/metabolism; Interleukin-1beta/immunology; 90-kDa/metabolism
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1beta stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient. Human chondrocytes treated with IL-1beta resulted in robust Nrf2/ARE reporter activity, which was inhibited by pretreatment with antioxidants indicating that Nrf2 activity was due to IL-1beta-induced ROS generation. Ectopic expression of Nrf2 significantly suppressed the IL-1beta-induced generation of ROS while Nrf2 knockdown significantly increased the basal as well as
Khan Nazir M; Ahmad Imran; Haqqi Tariq M
Free radical biology & medicine
2018
2018-02
<a href="http://doi.org/10.1016/j.freeradbiomed.2018.01.013" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2018.01.013</a>
Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis.
*Apoptosis; *ERK1/2; *Nrf2; *Osteoarthritis; *Redox
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1beta stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient. Human chondrocytes treated with IL-1beta resulted in robust Nrf2/ARE reporter activity, which was inhibited by pretreatment with antioxidants indicating that Nrf2 activity was due to IL-1beta-induced ROS generation. Ectopic expression of Nrf2 significantly suppressed the IL-1beta-induced generation of ROS while Nrf2 knockdown significantly increased the basal as well as
Khan Nazir M; Ahmad Imran; Haqqi Tariq M
Free radical biology & medicine
2018
2018-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.freeradbiomed.2018.01.013" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2018.01.013</a>
Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes.
*ERK1/2; *Nrf2; *Osteoarthritis; *Redox; *Wogonin; Anti-Inflammatory Agents/administration & dosage; Chondrocytes/drug effects/pathology; Flavanones/*administration & dosage; Gene Expression Regulation/drug effects; Humans; Inflammation/*drug therapy/metabolism/pathology; Kelch-Like ECH-Associated Protein 1/chemistry/*genetics/metabolism; MAP Kinase Signaling System/drug effects; Molecular Docking Simulation; NF-E2-Related Factor 2/antagonists & inhibitors/chemistry/*genetics/metabolism; Osteoarthritis/*drug therapy/metabolism/pathology; Protein Binding; Reactive Oxygen Species/metabolism; Signal Transduction/drug effects
Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis. Here, we evaluated the potential chondroprotective and anti-inflammatory effects of Wogonin, a naturally occurring flavonoid, in IL-1beta-stimulated human OA chondrocytes and cartilage explants. Wogonin completely suppressed the expression and production of inflammatory mediators including IL-6, COX-2, PGE2, iNOS and NO in
Khan Nazir M; Haseeb Abdul; Ansari Mohammad Y; Devarapalli Pratap; Haynie Sara; Haqqi Tariq M
Free radical biology & medicine
2017
2017-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.freeradbiomed.2017.02.041" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2017.02.041</a>