Qun Chen1, Xibin Kao2, Yan Gao3, Jinghong Chen4, Zhaoheng Dong5, Chen Chen6. 1. Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. chenqun2003076@163.com. 2. Institute for Hygiene of Ordnance Industry, Xi'an, 710061, Shaanxi, People's Republic of China. 3. Institute of Health Supervision, Beilin District, Xi'an, 710003, Shaanxi, People's Republic of China. 4. Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. 5. Shandong Shenghua Electronic New Materials Co., Ltd, Yantai, Shandong, China. 6. Endocrinology, Faculty of Medicine, School of Biomedical Sciences,, University of Queensland, Brisbane, Australia.
Abstract
BACKGROUND: Nitric oxide (NO) and reactive oxygen species (ROS) play an important role in the pathology of human osteoarthritis (OA). Ankylosing spondylitis (AS) and atypical OA have similar clinical manifestations and often require differential diagnosis. The mechanism is however not totally clear yet. This study aims to investigate the effects of excessive NO-ROS in OA patients and the effects of extracellular signal-regulated kinases (ERK) pathway in NO-induced apoptosis of chondrocytes during OA progress. METHODS AND RESULTS: Serum samples from OA or AS as pathological control patients and healthy controls were collected for NO and related chemical measurements. The rabbit articular chondrocytes were cultured in vitro, and NO was applied by Sodium Nitroprusside (SNP) in culture medium to mimic OA condition in patients. The level of SNP-evoked chondrocyte apoptosis with or without PD98059 (ERK-specific inhibitor) was evaluated by TUNEL assay, Annexin V flow cytometry and Western blotting. The activity and mRNA expression of caspase-3 in chondrocytes were measured by assay kits and RT-PCR. The levels of NO and malondialdehyde (MDA) in serum were significantly higher in OA patients, while only MDA was significantly higher in AS patients. However, the level of superoxide dismutase (SOD) was lower in both OA and AS patients. SNP induced chondrocyte apoptosis was enhanced by PD98059 with increased protein expression and functional activity of caspase-3. CONCLUSIONS: The increase in nitric oxide occurs specifically in OA patients. ERK pathway may play a protective role on the NO-induced chondrocyte apoptosis, and inhibition of ERK pathway enhances the NO-induced apoptosis.
BACKGROUND: Nitric oxide (NO) and reactive oxygen species (ROS) play an important role in the pathology of human osteoarthritis (OA). Ankylosing spondylitis (AS) and atypical OA have similar clinical manifestations and often require differential diagnosis. The mechanism is however not totally clear yet. This study aims to investigate the effects of excessive NO-ROS in OA patients and the effects of extracellular signal-regulated kinases (ERK) pathway in NO-induced apoptosis of chondrocytes during OA progress. METHODS AND RESULTS: Serum samples from OA or AS as pathological control patients and healthy controls were collected for NO and related chemical measurements. The rabbit articular chondrocytes were cultured in vitro, and NO was applied by Sodium Nitroprusside (SNP) in culture medium to mimic OA condition in patients. The level of SNP-evoked chondrocyte apoptosis with or without PD98059 (ERK-specific inhibitor) was evaluated by TUNEL assay, Annexin V flow cytometry and Western blotting. The activity and mRNA expression of caspase-3 in chondrocytes were measured by assay kits and RT-PCR. The levels of NO and malondialdehyde (MDA) in serum were significantly higher in OA patients, while only MDA was significantly higher in AS patients. However, the level of superoxide dismutase (SOD) was lower in both OA and AS patients. SNP induced chondrocyte apoptosis was enhanced by PD98059 with increased protein expression and functional activity of caspase-3. CONCLUSIONS: The increase in nitric oxide occurs specifically in OA patients. ERK pathway may play a protective role on the NO-induced chondrocyte apoptosis, and inhibition of ERK pathway enhances the NO-induced apoptosis.
Authors: Rennie G Howard; Jonathan Samuels; Soterios Gyftopoulos; Svetlana Krasnokutsky; Joseph Leung; Christopher J Swearingen; Michael H Pillinger Journal: J Clin Rheumatol Date: 2015-03 Impact factor: 3.517
Authors: Carlo Alberto Paggi; Amel Dudakovic; Yao Fu; Catalina Galeano Garces; Mario Hevesi; Daniela Galeano Garces; Allan B Dietz; Andre J van Wijnen; Marcel Karperien Journal: Cartilage Date: 2020-07-22 Impact factor: 4.634