Endothelial dysfunction contributes to chondrocyte senescence associated with Insulin-like growth factor-binding protein-6 in a spontaneously hypertensive rat model

Given an epidemiological association between hypertension and osteoarthritis (OA), we aim to elucidate how vascular pathology triggers avascular articular cartilage loss by comparing vascular and joint phenotype between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Endothelial molecular changes were delineated via bulk RNAseq. Transcriptomic analyses of rat endothelial cells revealed upregulated insulin-like growth factor-binding proteins (IGFBPs). Among them, IGFBP6 was identified to induce chondrocyte senescence in vitro, highlighting a potential therapeutic target for preventing joint structural damage by addressing endothelial dysfunction. Primary endothelial cells were isolated from 3-month-old WKY and SHR, specifically the proximal segment of the aorta adjacent to the heart (n=3 per group). Aortas were dissected from the hearts of 3-month-old rats and cut into pieces, then placed with the endothelium side down in 12-well plates. Total RNA was later extracted from primary endothelial cells.