SUMOylated GLUT1 inhibited the glycometabolism disorder in chondroctyes during osteoarthritis

Reduction of glucose transporter 1 (GLUT1), even deletion, may results in cartilage fibrosis and osteoarthritis. This study aims to investigate the SUMOylation of GLUT1 in osteoarthritis through small ubiquitin-like modifier 1(SUMO1), and explore the role of SUMOylated GLUT1 in glycometabolism, proliferation and apoptosis in chondrocytes. Human chondrocytes were incubated with 10 ng/mL of IL-1β to mimic osteoarthritis in vitro. GLUT1, SUMO1 and Chondrocyte-related genes including COL2A1, MMP13 and ADAMTS4 were evaluated using western blot. Cell viability and cell apoptosis of chondrocytes were measured by cell counting kit-8 assay and flow cytometry, respectively. The changes in glycometabolism were evaluated using extracellular acidification rate (ECAR) and glucose uptake assay. Co-immunoprecipitation (Co-IP) was used to verify the interaction between GLUT1 and SUMO1. The stabilization role of SUMO1 in GLUT1 was determined by cycloheximide assay. IL-1β induced the decrease of GLUT1, cell viability, ECAR, glucose uptake and COL2A1 and the increase of cell apoptosis, MMP13 and ADAMTS4 in chondrocytes. However, overexpression of SUMO1 led to the reduction of cell apoptosis, MMP13 and ADAMTS4 and the elevation of GLUT1, cell viability, ECAR, glucose uptake and COL2A1 in IL-1β-stimulated chondrocytes. There was SUMOylation sites on GLUT1. Intriguingly, SUMO1 was significantly enriched in GLUT1 using Co-IP assay, and stabilized GLUT1 in chondrocytes. SUMO1-mediated SUMOylation is capable of stabilizing GLUT1 to inhibit glycometabilsm disorder and cell apoptosis in IL-1β-stimulated chondrocytes.