Konečné produkty pokročilé glykaceu pacientů s osteoartrózou a revmatoidníartritidou a jejich potenciální úlohav patogenezi těchto onemocnění

Advanced glycation endproducts in osteoarthritis andrheumatoid arthritis patients and their potential role in pathogenesis of these diseases

The review is aimed at the well-known chronic musculosceletal disorders, osteoarthritis (OA) andrheumatoid arthritis (RA), and their increasing incidence during ageing. Especially, collagen typeII undergoes age-related non-enzymatic covalent modification (NECM), advanced glycation endproducts(AGE) form, which then accumulate in the articular cartilage. Increased cartilage accumulationof AGE results in cartilage quality alteration and decreases its mechanical damage resistance.This finally contributes to degeneration of collagen fibril network and to initiation and/or progressionof joint damage. The molecular events of AGE formation represent reactive oxo-group of thesugar and amino-group of the target molecule condensation (so-called Maillard reaction). Thisreaction is potentiated by hyperglycemia and oxidative stress. Increased tissue accumulation ofAGE is seen not only during the natural process of aging but also during different pathologicconditions (e.g. diabetes, renal insufficiency, some inflammatory and primary degenerative disorders).AGE role in the inflammatory cell response or even in the initiation of the complex autoimmuneprocess in RA has been considered in recent years. Special cell receptor for AGE (RAGE) isimportant for inflammatory cell activation and the presence ofRAGEon many cell types has alreadybeen described. This paper also points at AGE presence in body fluids and tissues, at the usefulnessof their detection to follow up the disease activity of various disorders, at the attempts to elucidatepathogenesis of these disorders, and also at the utility of AGE inhibitors, which could be of potentialsignificance slowing the disease progression.

Key words:
osteoarthritis (OA),rheumatoid arthritis (RA), non-enzymatic covalent modification(NECM), Maillard reaction, advanced glycation endproducts (AGE),