Hypertension meets osteoarthritis — revisiting the vascular aetiology hypothesis

Abstract

Osteoarthritis (OA) is a whole-joint disease characterized by subchondral bone perfusion abnormalities and neovascular invasion into the synovium and articular cartilage. In addition to local vascular disturbance, mounting evidence suggests a pivotal role for systemic vascular pathology in the aetiology of OA. This Review outlines the current understanding of the close relationship between high blood pressure (hypertension) and OA at the crossroads of epidemiology and molecular biology. As one of the most common comorbidities in patients with OA, hypertension can disrupt joint homeostasis both biophysically and biochemically. High blood pressure can increase intraosseous pressure and cause hypoxia, which in turn triggers subchondral bone and osteochondral junction remodelling. Furthermore, systemic activation of the renin–angiotensin and endothelin systems can affect the Wnt–β-catenin signalling pathway locally to govern joint disease. The intimate relationship between hypertension and OA indicates that endothelium-targeted strategies, including re-purposed FDA-approved antihypertensive drugs, could be useful in the treatment of OA. Hypertension and osteoarthritis are associated with each other epidemiologically and share several molecular pathways. In this Review, the authors examine the crossover between these two conditions and propose the repurposing of antihypertensive medications to treat osteoarthritis. Epidemiologically, high blood pressure (hypertension) has been linked to radiographic and symptomatic knee osteoarthritis. At the tissue level, systemic hypertension leads to subchondral bone perfusion abnormalities and ischaemia, which disrupts angiogenic–osteogenic coupling and impairs the integrity of the bone–cartilage functional unit. At the molecular level, systemic activation of the renin–angiotensin, endothelin and Wnt–β-catenin signalling pathways induces a phenotypical change in articular chondrocytes and triggers cartilage degradation. Antihypertensive medications that exhibit chondroprotective effects in preclinical studies warrant further investigation in patients with osteoarthritis and the frequently encountered comorbidity of systemic hypertension. Epidemiologically, high blood pressure (hypertension) has been linked to radiographic and symptomatic knee osteoarthritis. At the tissue level, systemic hypertension leads to subchondral bone perfusion abnormalities and ischaemia, which disrupts angiogenic–osteogenic coupling and impairs the integrity of the bone–cartilage functional unit. At the molecular level, systemic activation of the renin–angiotensin, endothelin and Wnt–β-catenin signalling pathways induces a phenotypical change in articular chondrocytes and triggers cartilage degradation. Antihypertensive medications that exhibit chondroprotective effects in preclinical studies warrant further investigation in patients with osteoarthritis and the frequently encountered comorbidity of systemic hypertension.