Endothelial Dysfunction Contributes to Chondrocyte Senescence Associated With Insulin-Like Growth Factor-Binding...

Area of Science:

• Vascular Biology
• Rheumatology
• Molecular Biology

Background:

• Epidemiological studies link hypertension and osteoarthritis.
• Vascular pathology is implicated in avascular articular cartilage loss.

Purpose of the Study:

• To elucidate how vascular pathology triggers articular cartilage loss.
• To compare vascular and joint phenotypes in spontaneously hypertensive rats versus normotensive Wistar Kyoto rats.
• To investigate the molecular mechanisms linking endothelial dysfunction to osteoarthritis.

Main Methods:

• Assessed endothelial function via blood pressure monitoring and photoacoustic imaging.
• Evaluated joint damage using radiological and histological examination.
• Analyzed endothelial gene expression (RNA-seq) and secretome (proteomics) to identify key factors in chondrocyte senescence.
• Utilized captopril to test therapeutic potential in vitro and in vivo.

Main Results:

• Spontaneously hypertensive rats showed higher blood pressure, joint hypoxia, and endothelial oxidative stress earlier than controls.
• Endothelial dysfunction preceded structural joint damage.
• Osteoarthritis-like pathology, including senescent chondrocytes and cartilage degradation, was observed in hypertensive rats and mitigated by captopril.
• IGFBPs, particularly IGFBP6, were upregulated in endothelial cells and induced chondrocyte senescence.

Conclusions:

• Systemic vascular dysfunction, characterized by endothelial dysfunction and IGFBP upregulation (e.g., IGFBP6), contributes to joint damage and osteoarthritis.
• Targeting endothelial dysfunction presents a potential therapeutic strategy for preventing joint structural damage.