Synovial fluid glycoproteome profiling in knee osteoarthritis: Molecular insights into type 2 diabetes-associated biomarkers and therapeutic targets

Abstract

Type 2 diabetes mellitus (T2DM) and Osteoarthritis (OA) share common risk factors like age, obesity and hypertension. Currently, 52 % of diabetic patients suffer from arthritis. Diabetes facilitates OA by altering lipid metabolism, levels of adipokines & cytokines, accumulation of advanced glycation end products, etc., which affects cartilage & bone health. However, the molecular mechanisms of the association of OA with T2DM remain unexplored. Since diabetes greatly affects the glycosylation status of proteins, the present study focused on identifying glycoproteins that could serve as diagnostic and prognostic markers for identifying osteoarthritis in diabetic individuals by LC-MS/MS. Comparative proteomic analysis revealed 20 significantly altered glycoproteins; among them, thyroxine-binding globulin (THBG), alpha-1-antitrypsin (A1AT), fibrinogen gamma chain (FGG) and angiotensinogen (AGT) were further validated. THBG, A1AT and AGT showed promising potential to identify the comorbid condition in serum and synovial fluid, however, ROC analysis identified THBG as the best candidate glycoprotein marker. Upregulation of THBG in OADM disrupts the bone remodeling cycle, degrades insulin, and promotes the expression of GLUT-1 and MMP-9. Overall, THBG could also serve as a therapeutic target for reducing the progression of osteoarthritis and alleviating pain and bone stiffness associated with the disease.