H G Lee1, J H Yang. 1. Department of Pharmacology and Toxicology, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
Abstract
OBJECTIVE: Chondrocyte apoptosis represents an important component in the osteoarthritis (OA) pathogenesis. This study sought to investigate the potential of polychlorinated biphenyl (PCB)126, the most potent and ubiquitous environmental pollutant of PCB congeners, on chondrocyte apoptosis and its mechanism of action. METHODS: Rabbit articular chondrocytes cultured from tibial and femoral in cartilage were exposed to PCB126. Productions of reactive oxygen species (ROS) and nitric oxide (NO) and nuclear factor-kB (NF-kB) binding activity were measured. After 24 h exposure to PCB126, the apoptotic cell death was detected by caspase-3 activity, enzyme-linked immunosorbent assay (ELISA) using antibodies against DNA and histone, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) staining. RESULTS: PCB126 generated ROS, which was blocked by the antioxidants (N-acetylcystein and trolox), or the aryl hydrocarbon receptor (AhR) inhibitor, α-naphthoflavone (α-NF). PCB126 exposure also increased NO production and NF-kB binding activity in the chondrocytes, which were blocked by the iNOS inhibitor, N-monomethyl-l-arginine (l-NMMA). All apoptosis detection techniques used in this study revealed an increase of apoptotic effects by PCB126 exposure, which was blocked by inhibitors of ROS or iNOS. This is the first report to demonstrate the potential of a PCB congener to induce chondrocytes apoptosis, which could be an initial process in cartilage degradation. CONCLUSIONS: PCB may be an initiator of chondrocyte apoptosis, which is closely linked to degradation of cartilage in OA pathogenesis. This study may contribute to identifying the possible causes of arthritis in our environment.
OBJECTIVE: Chondrocyte apoptosis represents an important component in the osteoarthritis (OA) pathogenesis. This study sought to investigate the potential of polychlorinated biphenyl (PCB)126, the most potent and ubiquitous environmental pollutant of PCB congeners, on chondrocyte apoptosis and its mechanism of action. METHODS:Rabbit articular chondrocytes cultured from tibial and femoral in cartilage were exposed to PCB126. Productions of reactive oxygen species (ROS) and nitric oxide (NO) and nuclear factor-kB (NF-kB) binding activity were measured. After 24 h exposure to PCB126, the apoptotic cell death was detected by caspase-3 activity, enzyme-linked immunosorbent assay (ELISA) using antibodies against DNA and histone, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) staining. RESULTS:PCB126 generated ROS, which was blocked by the antioxidants (N-acetylcystein and trolox), or the aryl hydrocarbon receptor (AhR) inhibitor, α-naphthoflavone (α-NF). PCB126 exposure also increased NO production and NF-kB binding activity in the chondrocytes, which were blocked by the iNOS inhibitor, N-monomethyl-l-arginine (l-NMMA). All apoptosis detection techniques used in this study revealed an increase of apoptotic effects by PCB126 exposure, which was blocked by inhibitors of ROS or iNOS. This is the first report to demonstrate the potential of a PCB congener to induce chondrocytes apoptosis, which could be an initial process in cartilage degradation. CONCLUSIONS:PCB may be an initiator of chondrocyte apoptosis, which is closely linked to degradation of cartilage in OA pathogenesis. This study may contribute to identifying the possible causes of arthritis in our environment.
Authors: Dima W Alhamad; Husam Bensreti; Jennifer Dorn; William D Hill; Mark W Hamrick; Meghan E McGee-Lawrence Journal: J Mol Endocrinol Date: 2022-08-22 Impact factor: 4.869
Authors: Helen C Poynton; Simone Hasenbein; Joshua B Benoit; Maria S Sepulveda; Monica F Poelchau; Daniel S T Hughes; Shwetha C Murali; Shuai Chen; Karl M Glastad; Michael A D Goodisman; John H Werren; Joseph H Vineis; Jennifer L Bowen; Markus Friedrich; Jeffery Jones; Hugh M Robertson; René Feyereisen; Alexandra Mechler-Hickson; Nicholas Mathers; Carol Eunmi Lee; John K Colbourne; Adam Biales; J Spencer Johnston; Gary A Wellborn; Andrew J Rosendale; Andrew G Cridge; Monica C Munoz-Torres; Peter A Bain; Austin R Manny; Kaley M Major; Faith N Lambert; Chris D Vulpe; Padrig Tuck; Bonnie J Blalock; Yu-Yu Lin; Mark E Smith; Hugo Ochoa-Acuña; Mei-Ju May Chen; Christopher P Childers; Jiaxin Qu; Shannon Dugan; Sandra L Lee; Hsu Chao; Huyen Dinh; Yi Han; HarshaVardhan Doddapaneni; Kim C Worley; Donna M Muzny; Richard A Gibbs; Stephen Richards Journal: Environ Sci Technol Date: 2018-04-24 Impact factor: 9.028