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.鉴于高血压与骨关节炎（osteoarthritis, OA）之间存在流行病学关联，本研究旨在通过对比自发性高血压大鼠（spontaneously hypertensive rats, SHR）与正常血压Wistar Kyoto（WKY）大鼠的血管表型与关节表型，阐明血管病理如何诱发无血管性关节软骨丢失。研究通过批量RNA测序（bulk RNAseq）明确了内皮细胞的分子变化特征。对大鼠内皮细胞的转录组分析显示，胰岛素样生长因子结合蛋白（insulin-like growth factor-binding proteins, IGFBPs）表达上调。其中，胰岛素样生长因子结合蛋白6（IGFBP6）被证实可在体外诱导软骨细胞衰老，这一发现凸显了通过改善内皮功能障碍预防关节结构损伤的潜在治疗靶点。