PMS13 - Study On Mechanism Of Type 2 Deiodinase Gene And Erk Signal Transduction In Kashin-Beck Disease

Abstract

Kashin-Beck disease (KBD) is an endemic, deformable, and chronic osteoarthropathy prevailing in selenium (Se)-deficiency regions, while its etiopathogenesis maintains obscure. Type 2 Deiodinase (DIO2) is an important Se-dependent antioxidant enzyme and there are many polymorphisms in DIO2 gene, among which, Thr92Ala（rs225014）has been studied widespread in diseases. In many different cells, ERK signalling pathway palys a role in anti-apoptosis and decreased ERK activity is necessary for apoptosis. Therefore, we investigated possible association between DIO2 Thr92Ala and susceptibility to KBD in a Chinese population.To explore molecular mechanism of cartilage apoptosis and role of Se in prevention in KBD, expression of signal molecules of ERK pathway in controls and KBD patients are detected and Na2SeO3 are added to explore it’s effect on ERK pathway. 218 KBD patients and 209 age and sex matched controls were enrolled and served as KBD and control group respectively. Polymerase Chain Reaction-Restriction Fragment Length Polymophism (PCR-RFLP) is used to analyze DIO2 Thr92Ala polymorphism. Real-Time PCR is used to detect DIO2 mRNA. Western-blot is used to detect expression of signal molecules of ERK transduction pathway. No difference were found in genotypic and allelic frequency of DIO2 Thr92Ala between KBD and control group (P>0.05). DIO2 mRNA level of cartilage tissue was significantly different between KBD and controls (P<0.05). Expression of pRaf-1, pMek1/2 and pErk1/2 decreased significantly in KBD patients (0.72~, 0.78~ and 0.28 fold respectively, P<0.05) compared with controls. no association was found between DIO2 Thr92Ala polymorphism and KBD incidence. Expression of DIO2 mRNA in KBD patients decreased significantly coampared with controls. Changes of apoptosis-related molecules on ERK signaling pathway in KBD patients suggested that ERK signaling pathway might play important roles in molecular biology mechanism of KBD, and Na2SeO3 could promote activation of pRaf-1，pMek1/2 and pErk1/2. *This research is supported by National Natural Science Foundation (No. 30671820，81172610).