An international team of researchers, led by the University of Surrey, UK, has identified a crucial link between metabolism and osteoarthritis.
Phenotypes of osteoarthritis: evidence suggests that patients with osteoarthritis fall into multiple phenotypic subgroups defined on the basis of the main driver of disease, one of which is a distinct metabolic phenotype, although all osteoarthritis phenotypes probably involve metabolic alterations; cartilage, bone and synovium are all affected by external and internal drivers of disease such as inflammation, injury or biomechanical alterations, metabolic reprogramming and immunomodulation, but different synovial joint tissues dominate the disease in different patients with osteoarthritis. Image credit: Mobasheri et al / Nature Reviews Rheumatology, doi: 10.1038/nrrheum.2017.50.
Osteoarthritis is the most common form of arthritis in the United States, affecting millions of adults.
It’s a chronic joint disease that breaks down cartilage in the neck, lower back, knees, hips, shoulders, and/or fingers. Common symptoms are pain, stiffness, and limited joint movement.
Currently there is no effective treatment for this painful ailment, with only painkillers available to treat symptoms and no known cure.
“For too long osteoarthritis has been known as the ‘wear and tear disease’ and it has been assumed that it is part and parcel of getting older,” said Ali Mobasheri, a professor of musculoskeletal physiology at the University of Surrey and lead author of the review published in the April 6 issue of the journal Nature Reviews Rheumatology.
“However, this is not the case and what we have learnt is that we can control and prevent the onset of this painful condition.”
Factors underlying metabolic alterations in osteoarthritis: poor diet and lifestyle choices can contribute to weight gain and lead to obesity; ageing, obesity and other co-morbidities associated with osteoarthritis contribute to metabolic reprogramming in a variety of cells and tissues, leading to inflammaging and cellular senescence, which in turn cause further changes in cellular metabolism in osteoarthritis. Image credit: Mobasheri et al / Nature Reviews Rheumatology, doi: 10.1038/nrrheum.2017.50.
Metabolic changes, caused by a poor diet and a sedentary lifestyle, trigger the genetic reprogramming of cells in the body and joints, Prof. Mobasheri and his colleagues from UK, Spain, France, the Netherlands and Ireland reported.
Such metabolic changes impact upon the cells ability to produce energy, forcing it to generate alternative sources to function.
The stress this places on cells leads to the overproduction of glucose, which when not used for energy transforms into lactic acid, which is difficult for the body to flush out.
Abnormal levels of this acid in the body leads to the inflammation of the joint’s cartilage which impedes on movement and causes pain.
By identifying metabolic changes in cells, it is potentially possible to control or significantly slow down the symptoms of osteoarthritis, alleviating the suffering of millions of people.
Metabolism in homeostatic chondrocytes: in healthy joints, chondrocytes utilize glucose as well as other metabolic fuels and sources of energy; glucose utilization via glycolysis and oxidative phosphorylation helps to maintain an optimal level of mitochondrial function and biogenesis; the metabolism of healthy chondrocytes is therefore optimized to maintain normal energy homeostasis via signaling through the AMPK–SIRT1–PGC1? pathway. AMPK – AMP-activated protein kinase; ETC – electron transport chain; GLUT1 – glucose transporter type 1; PGC1? – peroxisome proliferator-activated receptor ? co-activator 1?; ROS – reactive oxygen species; SIRT1 – NAD-dependent protein deacetylase sirtuin-1; TCA – tricarboxylic acid. Image credit: Mobasheri et al / Nature Reviews Rheumatology, doi: 10.1038/nrrheum.2017.50.
Altered metabolism in chondrocytes in osteoarthritis: chondrocytes in osteoarthritis switch from oxidative phosphorylation to glycolysis as their main source of energy metabolism; in osteoarthritic joints, chondrocytes are exposed to proinflammatory cytokines and microenvironmental alterations, including hypoxia and nutrient stress; mitochondrial metabolism is impaired and reactive oxygen species accumulate, causing damage to mitochondria which inhibits AMPK signaling and activity, downregulate SIRT1 and decrease levels of PGC1?, the master regulator of mitochondrial biogenesis. AMPK – AMP-activated protein kinase; ETC – electron transport chain; GLUT1 – glucose transporter type 1; PGC1? – peroxisome proliferator-activated receptor ? co-activator 1?; SIRT1 – NAD-dependent protein deacetylase sirtuin-1; TCA – tricarboxylic acid. Image credit: Mobasheri et al / Nature Reviews Rheumatology, doi: 10.1038/nrrheum.2017.50.
“It is important never to underestimate the significance of a healthy diet and lifestyle as not only does it impact upon our general wellbeing but can alter the metabolic behavior of our cells, tissues and organs leading to serious illnesses,” Prof. Mobasheri said.
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Ali Mobasheri et al. 2017. The role of metabolism in the pathogenesis of osteoarthritis. Nature Reviews Rheumatology 13: 302-311; doi: 10.1038/nrrheum.2017.50
