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.
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.
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The work of the authors is supported by the Research Grants Council of Hong Kong Early Career Scheme (PolyU 251008/18M) and General Research Fund (15106120), the PROCORE-France/Hong Kong Joint Research Scheme (F-PolyU504/18), the Health and Medical Research Fund Scheme (#01150087, #15161391 and #16172691), and the Project of Strategic Importance at The Hong Kong Polytechnic University (all grants awarded to C.W.).
The authors declare no competing interests.
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- T2 values
Values obtained in MRI scans that provide information about the water content and organization of the collagen structure in cartilage.
- Metaphyseal bone
The transition zone between the shaft and head of long bones; it is the location of the growth plate, which elongates and grows during bone development.
- Diaphyseal bone
The midsection of long bones, composed of tubular cortical bone on the outside and a hollow bone marrow cavity on the inside.
- Areolar tissue
A type of connective tissue with loosely organized fibres that provides space for interstitial fluid to fill the tissue to provide nourishment.
The ends of long bones that are covered with articular cartilage and join adjacent bones.
- Weibel–Palade bodies
Storage granules in endothelial cells that can be released through exocytosis.
A situation of electrolyte imbalance with low potassium in blood serum.
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Ching, K., Houard, X., Berenbaum, F. et al. Hypertension meets osteoarthritis — revisiting the vascular aetiology hypothesis. Nat Rev Rheumatol 17, 533–549 (2021). https://doi.org/10.1038/s41584-021-00650-x