Abstract
Aim
This aim of this study was to investigate apoptosis, reactive oxygen species (ROS), and their upstream markers in Anteromedial Gonarthrosis (AMG).
Methods
Ten resection specimens, from patients undergoing unicompartmental knee replacement for AMG, and ten control specimens, collected from vascular disease patients undergoing above knee amputation, were used. Routine histology and immunohistochemical studies were conducted for Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Active Caspase 3, Cytochrome C, Active Bax, Bim, 3-Nitrotyrosine and Forkhead box O3A (FOXO 3A).
Results
Cell death was shown predominantly in the surface layer of chondrocytes of damaged cartilage (p<0.001). There was a significant difference in TUNEL staining between regions (p=0.001). This ranged from 26% (most damaged) to 4% (undamaged) and was significantly higher (p<0.001) in AMG compared to the control samples which showed an average of 2% TUNEL overall.
Upstream markers of apoptosis (Active Caspase 3, Cytochrome C, Active Bax), assessed qualitatively, were present in a similar distribution to that of TUNEL staining.
3-Nitrotyrosine, an indicator of ROS mediated damage, was also shown to be a predominantly surface phenomenon. There was a significant difference (p<0.001) between regions, ranging from 58% (most damaged) to 10% (undamaged). Again, this was significantly higher that the control samples (p<0.001). In line with indicators of ROS mediated damage, Bim and FOXO3A were also detected.
Discussion
In AMG, apoptosis and ROS appear to be a part of the biological process leading to cartilage degeneration. Such cellular responses in ‘stressed’ chondrocytes provide possible targets for disease modification, thus delaying or preventing the need for joint arthroplasty. Further work is required to demonstrate these pathways and the effects of intervention.
