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Urolithin A improves reduces cartilage degeneration and pain in osteoarthritis

Osteoarthritis (OA) is the most common age-related joint disorder, affecting over 500 million people worldwide. Mitochondrial dysfunction plays a key role in the development of OA; however, interventions focused on mitochondrial health are not currently available. This trial demonstrated that Urolithin A improved mitophagy and mitochondrial health in joint cells from people with OA. In mouse models, UA reduced OA progression. The results support the ability of UA to act as a potential agent to improve mobility in joints damaged by OA.

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October 26, 2022

Key takeaways

Mitochondrial decline and reduced levels of mitophagy are commonly seen in cells of the cartilage (chondrocytes), contributing to the progression of osteoarthritis


Osteoarthritis (OA) is the most common age-related joint condition impacting millions of people worldwide. Despite its widespread prevalence and impact, there are no therapies that modify disease progression. The only pharmacological intervention currently available is pain management.

OA disease progression occurs as the joint tissue becomes damaged. Chondrocytes are a specific type of cell found in cartilage and mitochondrial decline is commonly seen in these cells. The ability to remove damaged mitochondria to generate new ones is called mitophagy and this process is often impaired in the chondrocytes.

Finding ways to target mitophagy in osteoarthritic cells could be a strategy to for OA treatment, and to date, no investigations have been conducted.

The purpose of this study was to examine the impact of Urolithin A (UA) on the mitochondria in knee cells taken from healthy humans and those with OA. The researchers also assessed the role UA played in cartilage degradation, inflammation and pain in mouse models of OA. Additionally they measured biomarkers of mitophagy and mitochondrial health in osteoarthritic joints treated with UA.

Methods/Study Design

To study the impact of UA on the mitochondria in the joints, the researchers collected chondrocytes from the knees of both healthy individuals and those with OA and analyzed them using as series of mitochondrial assays.

Next the researchers tested UA’s effects in experimental models of OA in rodents. Mice underent knee surgery or a sham surgery, and were fed either a standard diet or a diet supplemented with UA for 8 weeks at two different doses. At the end of the study knee sections were collected for examination.

Pain response was tested in mice by examining their response to a painful stimulus after 4 and 8 weeks of UA treatment.


UA administration increased both mitochoindrial function and mitophagy in healthy human chodrocytes. In the chondrocytes of healthy human knees, 24 hours of UA administration induce mitophagy and mitochondrial function without increasing the amount of mitochondria in the cell.

UA increased mitochondrial health in chondrocytes with OA. At the start, mitochonidral function was lower in diseased cells than it was in healthy cells. Administration of UA in these diseased chondrocytes led to a significant increase in mitochondrial function.

UA protected against cartilage deterioration in models of UA. In mouse models of osteoarthritis, UA treatment decreased the cartilige degredatoin in knee joints with OA.

Treatement with UA reduced inflammation and lessened pain. After 4 weeks of treatment, a decrease in pain response was seen in both groups of UA treated mice compared to those who did not recieve UA, and this improvement was even greater at 8 weeks. The data suggests that an even greater response could be seen from higher doses or longer treatments times. Inflammation is a key player on the progression of OA and the pain asosciated with this disease and in mouse models, UA was able to reduce inflammation.

UA increased mitophagy in OA models. Lastly, when looking at mouse models of OA, treatement with UA increased both the total concentration of mitochondria and the levels of mitophagy.


Decline in mitochondrial function plays an role in the progressoin of OA, yet there are no mitochondrial-targeting therapies to treat this disease. The results of this trial showed UA’s ability to increaes mitophagy in both healthy knee cells and knee cells with OA. Additionally, in mouse models of OA of the knee joint, UA was shown to improve mitochoindrial function, mitigate pain, and reduce inflammation.

Based on these resutls, future studies to examine the effect of UA on OA in clinical trials is warrented. As of now, UA is the only moleculr that has been successfuly tested preclinical trials such as this that improves mitochondrial function, decrease OA pain and reduces inflammation. With the lack of drug therapies for modifying the diseaes progresson of OA, it is imprtant to investigate novel strategies that can help people living with this debilitating condition.

These preclinical findings demonstrate the unique role UA could play in both the disease progresoin and symptomology OA.


Davide D'Amico,Merissa Olmer,Andréane M. Fouassier,Pamela Valdés,Pénélope A. Andreux,Chris Rinsch,Martin Lotz

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