Helal Endisha
Postdoctoral researcher Dr. Helal Endisha is excited by the possibilities. "Leading a study like this where I am able to show that there is perhaps a light at the end of the tunnel, is simply amazing." (Photo: UHN)

One out of every six Canadians is currently living with osteoarthritis, a painful and debilitating form of arthritis affecting the cartilage surrounding the bones in your hips, knees, hands and spine.

By 2035, that number is expected to increase to one in four, with a new diagnosis every 60 seconds.

No treatment currently exists for osteoarthritis that can slow or stop the disease.

It has always been thought that increased weight puts strain on joints and that this is what causes osteoarthritis. Now, scientists from the Schroeder Arthritis Institute at UHN have discovered a surprising new molecular link between obesity, diet and osteoarthritis that could have impact for future treatment options.

"We have identified a small molecule that is increased in the blood and joint tissues of osteoarthritis patients, especially those who are obese," says Dr. Helal Endisha, first author of the study and researcher at the Schroeder Arthritis Institute.

If this molecule can be blocked, it has the potential to slow the progression of the disease, particularly in the high-risk obese population.

In a study published in the March 2021 issue of Arthritis and Rheumatology, the research team led by Dr. Mohit Kapoor, Co-Director of the Schroeder Arthritis Institute and the Tony and Shari Fell Platinum Chair in Arthritis Research, found that when cells from the joints of osteoarthritis patients were treated with increased levels of the small molecule (called microRNA 34a-5p), the cells produced harmful factors associated with joint destruction and inflammation.

On the other hand, patient joint cells treated with a blocker against this molecule produced more of the building blocks required for healthy joint tissues.

Next step developing targeted therapy for obese patients

Overall, this study has identified a molecule that is elevated in joint tissues as well as blood of osteoarthritis patients, especially patients who are obese.

"This is a population of patients who are at-risk of not only of developing osteoarthritis at an earlier age, but also a more severe and rapidly progressing form of the disease," says Dr. Rajiv Gandhi, an orthopedic surgeon within the Division of Orthopedics at the Schroeder Arthritis Institute.

Using patient cells and pre-clinical models of obesity and osteoarthritis, the study shows that blocking this molecule is able to reduce the severity of joint damage in obese pre-clinical models.

"The next step is to develop a targeted therapy for obese patients that will halt the rapid progression of osteoarthritis," says Dr. Kapoor.

This could lead to the development of a pharmacological treatment that can block this molecule through an injection into the knee joint. It would then bind to the microRNA 34a-5p and stop it from performing its joint destructive effects. More studies looking at the levels of microRNA 34a-5p in the blood could act as a diagnostic biomarker.

For Dr. Endisha, who completed her PhD in Dr. Kapoor's lab, working on this research is a dream come true.

"What really drew me to arthritis research is the opportunity to be involved with discovering a therapy that can cure an incurable disease," she says. "Leading a study like this where I am able to show that there is perhaps a light at the end of the tunnel, that there is the possibility of a treatment that could one day stop arthritis in its tracks and help people gain back control of their lives, is simply amazing."

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