Yitong Zhao1, Yuanxu Guo1, Mengyao Sun1, Safdar Hussion1, Ying Zheng2, Huang Huang1, Xinyu Huo1, Yutong Zhao3, Fujun Zhang1, Yan Han1, Qilan Ning1, Peng Xu4, Jian Sun5, Shemin Lu6. 1. Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University School of Basic Medical Sciences, West Yanta Street No.76, Xi'an, 710061, Shaanxi, People's Republic of China. 2. Department of Digestive Disease and Gastrointestinal Motility Research Room, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xi Wu Road, Xi'an, 710004, Shaanxi, People's Republic of China. 3. Department of Software Engineering, Xinjiang University School of Software, Urumqi, 830000, Xinjiang, People's Republic of China. 4. Department of Joint Surgery, Xi'an Honghui Hospital, Easter Youyi Road No. 555, Xi'an, 710054, Shaanxi, People's Republic of China. 5. Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University School of Public Health, West Yanta Street No.76, Xi'an, 710061, Shaanxi, People's Republic of China. sunjian1@xjtu.edu.cn. 6. Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University School of Basic Medical Sciences, West Yanta Street No.76, Xi'an, 710061, Shaanxi, People's Republic of China. lushemin@xjtu.edu.cn.
Abstract
INTRODUCTION: Selenium (Se) as well as selenoproteins are vital for osteochondral system development. Se deficiency (SeD) has a definite impact on the expression and activity of histone deacetylases (HDACs). Abnormal expression of some HDACs affects cartilage development. This current study aims to explore the relationship between differentially expressed HDACs and cartilage development, especially extracellular matrix (ECM) homeostasis maintenance, under SeD conditions. MATERIALS AND METHODS: Dark Agouti rats and C28/I2 cell line under SeD states were used to detect the differently expressed HDAC by RT-qPCR, western blotting and IHC staining. Meanwhile, the biological roles of the above HDAC in cartilage development and homeostasis maintenance were confirmed by siRNA transfection, western blotting, RNA sequence and inhibitor treatment experiments. RESULTS: HDAC2 exhibited lower expression at protein level in both animals and chondrocytes during SeD condition. The results of cell-level experiments indicated that forkhead box O3A (FOXO3A), which was required to maintain metabolic homeostasis of cartilage matrix, was reduced by HDAC2 knockdown. Meanwhile, induced HDAC2 was positively associated with FOXO3A in rat SeD model. Meanwhile, knockdown of HDAC2 and FOXO3A led to an increase of intracellular ROS level, which activated NF-κB pathway. Se supplementary significantly inhibited the activation of NF-κB pathway with IL-1β treatment. CONCLUSION: Our results suggested that low expression of HDAC2 under SeD condition increased ROS content by decreasing FOXO3A in chondrocytes, which led to the activation of NF-κB pathway and ECM homeostasis imbalance.
INTRODUCTION: Selenium (Se) as well as selenoproteins are vital for osteochondral system development. Se deficiency (SeD) has a definite impact on the expression and activity of histone deacetylases (HDACs). Abnormal expression of some HDACs affects cartilage development. This current study aims to explore the relationship between differentially expressed HDACs and cartilage development, especially extracellular matrix (ECM) homeostasis maintenance, under SeD conditions. MATERIALS AND METHODS: Dark Agouti rats and C28/I2 cell line under SeD states were used to detect the differently expressed HDAC by RT-qPCR, western blotting and IHC staining. Meanwhile, the biological roles of the above HDAC in cartilage development and homeostasis maintenance were confirmed by siRNA transfection, western blotting, RNA sequence and inhibitor treatment experiments. RESULTS: HDAC2 exhibited lower expression at protein level in both animals and chondrocytes during SeD condition. The results of cell-level experiments indicated that forkhead box O3A (FOXO3A), which was required to maintain metabolic homeostasis of cartilage matrix, was reduced by HDAC2 knockdown. Meanwhile, induced HDAC2 was positively associated with FOXO3A in rat SeD model. Meanwhile, knockdown of HDAC2 and FOXO3A led to an increase of intracellular ROS level, which activated NF-κB pathway. Se supplementary significantly inhibited the activation of NF-κB pathway with IL-1β treatment. CONCLUSION: Our results suggested that low expression of HDAC2 under SeD condition increased ROS content by decreasing FOXO3A in chondrocytes, which led to the activation of NF-κB pathway and ECM homeostasis imbalance.
Authors: Shireen Kassam; Heidi Goenaga-Infante; Lenushka Maharaj; Crispin T Hiley; Simone Juliger; Simon P Joel Journal: Cancer Chemother Pharmacol Date: 2011-04-26 Impact factor: 3.333
Authors: Nicole Metes-Kosik; Ivan Luptak; Patricia M Dibello; Diane E Handy; Shiow-Shih Tang; Hui Zhi; Fuzhong Qin; Donald W Jacobsen; Joseph Loscalzo; Jacob Joseph Journal: Mol Nutr Food Res Date: 2012-10-24 Impact factor: 5.914