AB0044 Nicotinamide Phosphoribosyltransferase in The Pathogenesis of Inflammation in Osteoarthritis

Abstract

BackgroundNicotinamide phosphoribosyltransferase (Nampt) is involved in various biological processes such as metabolism, stress response and the aging process.There are some data that TNF-α and other proinflammatory molecules may influence on exchange of NAD.Currently, there is no common understanding of the Nampt's role in the pathogenesis of joint diseases. The recent recearches of its participation in the processes of metabolism and inflammation support the hypothesis of involvement of this protein in the induction and maintenance of inflammation in osteoarthritis (OA). The presence of pseudogenes complicates Nampt investigation and enhance research bias.ObjectivesTo clarify the OA pathogenesis by examining serum concentrations of Nampt.MethodsWe observed 87 patients with various forms of OA aged 36 to 78 years, comparable with the group of healthy subjects (t =1,87 p>0.05).We used Althman R. D. criteria to diagnose OA (199). X-ray stages were evaluated using the Kellgren-Lawrence scale. Serum Nampt level was determined by ELISA with commercial test kits (RaiBiotech, cat No. EIA-VIS-1).ResultsWe assessed the level of Nampt in the serum of healthy individuals. The Median of Nampt normal values was 2,29 [Confidence interval (CI) =2,02 - 2,8] ng/ml. The Median Nampt level OA patients was 3,98 [CI =2,00 - 9,04] ng/ml, which was significantly higher than in normal subjects (p<0.001).Elevated levels of Nampt were revealed more often in patients with constant pain than in ones who had pain only on movement.The correlation coefficient between Nampt level and Lequesne functional index was equal to 0,4917 (p=0,041), with total index WOMAC - 0,589 (p=0,049).We notedsignificant statistical link between the Nampt's serum level and laboratory markers of inflammation in OA. Higher C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)concentrations were detected in patients with elevated Nampt level. Those facts indirectly confirm the anti-inflammatory properties of Nampt. These studies may support the hypotheses of Nampt's properties to influence on cytokines production, which are responsible for the maintenance of the inflammatory process in the synovium and the destruction of the cartilage.There are some data that Nampt inhibitors lead to downstream NF-kBinhibition, resulting in decreasing of intracellular level of nicotinamide adenine dinucleotide (NAD). So Nampt inhibitors may be used to suppress inflammation, for the treatment of diseases in which angiogenesis is involved, for the prevention and treatment of ischemia and other pathological states.Significant advances in molecular biology allow us to hope for the development of highly effective drugs that can delay the progression of OA and change his clinical course.ConclusionsThus, in our study the increased Nampt level was detected in 29% of OA patients. It's increasing is associated with secondary synovitis, elevated of ESR, CRP, with most severity of articular syndrome.The findings suggest the likely role Nampt in the pathogenesis of OA.ReferencesPathogen...