Osteoarthritis (Osteoarthritis, OA) is a chronic degenerative bone and joint disease that occurs in the middle-aged and elderly people, with joint pain and limited mobility as the main symptoms. The incidence of the disease is relatively high. There are about 500 million patients in the world. The prevalence of OA in people over 40 years old in China is about 46%, and the prevalence rate of people over 70 years old is about 62%. The etiology of
OA is not completely clear, and its occurrence is related to many factors such as age, obesity, joint strain, trauma, and genetics. As one of the most common chronic diseases, hypertension is also a common comorbidity of osteoarthritis. The close relationship between hypertension and osteoarthritis has attracted more and more attention. Current studies have found that hypertension can affect the occurrence and development of osteoarthritis through the following ways:
1. Change the local environment of joints
Although it is not yet fully understood, the systemic vascular disease caused by hypertension may lead to Disturbance of the local microenvironment of the joints.
First of all, hypertension impairs vascular function and increases intraosseous pressure, thereby reducing blood perfusion of joint local tissues. The reduction of local blood flow leads to subchondral bone ischemia and bone cell apoptosis, which in turn triggers bone resorption mediated by osteoclast .
Secondly, at least 50% of the necessary glucose and oxygen required by cartilage are provided by the capillaries of the subchondral bone. The reduction of local blood flow hinders the oxygen supply of the tissue, resulting in a hypoxic microenvironment that affects synovium tissue Metabolism and cause cartilage damage.
In addition, abnormal tissue perfusion caused by hypertension can lead to nutritional deficiencies in bones and cartilage. The decrease of glucose concentration in the extracellular matrix can weaken the anabolism mediated by insulin growth factor 1 in chondrocytes, leading to pathological changes in the joints. .
2. Affect the local structure of joints
When bone ischemia and hypoxic environment persist, bone cells will inevitably undergo apoptosis. Apoptotic bone cells induce neighboring bone cells to secrete RANKL to activate osteoclasts cell,Activated osteoclasts mediate bone resorption and even lead to osteonecrosis.
On the other hand, osteoclast-mediated bone resorption releases transforming growth factor-β (TGF-β), which stimulates the recruitment of mesenchymal stromal cells and further differentiates into osteoblasts, and osteoblasts initiate bone remodeling A cascade of reactions leads to sclerosis of the subchondral bone. In addition, hypoxia can also directly stimulate the differentiation of bone marrow mesenchymal stem cells into osteoblasts, which in turn leads to bone sclerosis of .
In addition, when the local tissues of the joint are hypoperfused, new blood vessels are widely generated compensatoryly, and the density of lymphatic vessels is reduced. These new blood vessels are highly permeable, and the secretion of joint synovial fluid increases and the return decreases, leading to joint effusion_ span12span.
3. Affecting common signal pathways
Cartilage is avascular. Compared with bone and synovium, it is less susceptible to direct physical stress and hypoxic stress caused by hypertension. However, hypertension can affect the fate of chondrocytes by activating some common signal pathways. At present, many researches mainly include the renin-angiotensin system (RAS), endothelin system and the classic Wnt-β-catenin pathway. These three pathways are all up-regulated in hypertension and induce chondrocyte hypertrophy and Inflammation reaction promotes joint catabolism.
At present, inhibitors of RAS, endothelin and Wnt signaling pathways and some existing antihypertensive drugs such as potassium-sparing diuretics and adrenaline antagonists have shown certain joint protection in some studies, but still need Further verification by clinical trials. In the future, with the deepening of the understanding of the two diseases and their interrelationships, new therapies to treat the two diseases at the same time will be expected to be discovered.
References:
1. Hunter, DJ, March, L. & Chew, M. Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet. 2020 Nov; 396(10264):1711-1712.
2. Niu, J., Clancy, M., Aliabadi, P., Vasan, R. & Felson, DT Metabolic syndrome, its components, and knee osteoarthritis: The Framingham Osteoarthritis Study. Arthritis Rheumatol. 2017 Jun; 69(6):1194 -1203.
3. Ching, K., Houard, X.,Berenbaum, F., Wen, CY. Hypertension meets osteoarthritis-revisiting the vascular aetiology hypothesis. Nat Rev Rheumatol. 2021 Sep; 17(9):533- 549.
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