TXNIP And Its Downstream Signals In Mediating Cartilage Degeneration Of Diabetes Mellitus Osteoarthritis

VObjective:This study intends to explore thioredoxin-interacting protein(TXNIP)expression in the diabetes mellitus osteoarthritis(OA)and its relationship with metabolism of cartilage.It further confirmed the relationship between diabetes mellitus and OA and clarified the role of TXNIP/GLUT-1 axis in diabetes mellitus OA.It aims to provide new ideas for the prevention and treatment of diabetes mellitus OA.Method:1.Immunohistochemical staining and WB were used to detect the expression of TXNIP in the cartilage tissue and synovial tissue of OA and diabetes mellitus OA;2.Seahorse experiment detect was used to detect the glycolytic(metabolic)ability of chondrocytes of OA and diabetes mellitus OA and chondrocytes under high glucose environment;3.WB was used to detect changes in the expression of TXNIP and glucose metabolism genes GLUT-1 in the present of different sugar concentrations and inflammatory stimulation;4.WB was used to detect the expression changes of TXNIP and glucose metabolism genes GLUT-1 after Knocked down/overexpressed TXNIP by small interfering RNA(si RNA)or overexpression plasmids,and seahorse experiment was used to detect the glycolysis of chondrocytes Metabolism changes in capacity;5.DMM(Destabilization of Medial Meniscus)used to mimic diabetes mellitus OA mice in diabetes mellitus OA mice(db/db)and control mice(m/m),and evaluate the progression of diabetes mellitus OA by weight,random blood glucose assessment and morphological staining;6.Micro-CT was used to evaluate the changes of subchondral bone in the diabetes mellitus OA mice;7.Immunohistochemical staining was used to detect the expression of TXNIP in the cartilage tissue of diabetes mellitus OA mice;Results:1.TXNIP was low expressed in diabetes mellitus OA cartilage tissues and diabetes mellitus OA cartilage cell models,the expression of glucose metabolism gene GLUT-1 was up-regulated,and the glycolytic(metabolism)capacity of diabetes mellitus OA cell models and cartilage tissues was enhanced;2.In chondrocytes,TXNIP reversely regulated the expression of the glucose metabolism gene GLUT-1 and the glycolytic(metabolic)ability of cell.3.In vivo animal experiments found that compared with OA mice,diabetes mellitus OA mice had significant synovial hyperplasia,cartilage abrasion and degeneration,subchondral bone loss was more serious,and TXNIP expression decreased significantly.Conclusion:1.The glycolytic ability of diabetes mellitus OA cartilage is higher than that of in OA cartilage;2.TXNIP affects the metabolism of chontrocytes in diabetes mellitus OA by negatived-regulating the expression of glucose metabolism genes GLUT-1;3.TXNIP mediates the cartilage degeneration of diabetes mellitus OA by regulating the metabolism of chondrocytes.