Abstract :
[en] Introduction
Osteoarthritis is the most common form of joint disease. It affects more than one million people in Belgium. Considered as a major public health problem among seniors, it is responsible for many direct and indirect costs generated, in particular, by the increasing number of hip and knee implants. To date, there is no way to detect early, predict or monitor the course of the disease. The association of glycated, oxidized and nitrated amino acids released from the joint with development and progression of knee osteoarthritis (OA) is unknown. We studied this in an OA animal model, patients with OA and interleukin-1β-activated human chondrocytes in vitro.
Material and methods
Sixty 3-week-old male Dunkin-Hartley guinea pigs were studied. At 4-week-old and 8 week intervals until week 36, twelve animals were sacrificed and histological severity of knee OA evaluated and cartilage rheological properties assessed. Human patients with early and advanced OA, and healthy controls were recruited. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin-1β. Serum, plasma and culture medium were analyzed for glycated, oxidized and nitrated amino acids.
Results
Severity of OA increased progressively in guinea pigs with age. Glycated, oxidized and nitrated amino acids were increased markedly at week 36, with glucosepane and dityrosine increasing progressively from weeks 20 and 28, respectively. Glucosepane correlated positively with OA histological severity (r = 0.58, p<0.0001) and Young’s Modulus (condyle: r = 0.52, plateau: r=0.56; p<0.0001), oxidation free adducts correlated positively with OA severity (p<0.0009). In clinical translation, plasma glucosepane was increased by 38% in early-stage OA (p<0.05) and 6-fold in patients with advanced OA (p<0.001), compared to healthy controls. Interleukin-1β increased the release of glycated and nitrated amino acids from chondrocytes in vitro.
Conclusions
In conclusion, we observed in our in vivo study an increase in rigidity as well as a decrease in the thickness of the cartilage during the aging of the animal. In addition, a decrease in average walking speed and swing speed in 36-week-old guinea pigs was observed with CatWalk analysis. Serum concentrations of glycation, oxidation and nitration products increased with the development of osteoarthritis. In vitro, IL-1β increased the concentration of AGE and 3-NT in human chondrocytes cultured in multilayers. Glucosepane, strongly correlated with the histological parameters as well as the mechanical properties of the cartilage is a potential biomarker for the detection and progression of osteoarthritis.
