Molecule Protects Cartilage From Damage During Osteoarthritis?

A team of scientists from Toronto and Calgary in Canada may provide a ray of hope for those experiencing the destruction of articular joints—whether knees or facet joints—by osteoarthritis (OA).

The study, “microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints,” was published in the Annals of the Rheumatic Diseases.

Co-author Mohit Kapoor, Ph.D. with the Arthritis Program, University Health Network, in Toronto, Canada, explained the study to OTW, “When we identified a molecule called microRNA-181a-5p back in 2016, we observed that it was present in high levels in the cartilage of patients with facet joint (spine) osteoarthritis and that it had an active role in the degeneration of cartilage. This sparked our interest to test if blocking this molecule could help in stopping the damage of cartilage in facet and knee joints.”

The authors wrote, “We used a variety of experimental models consisting of both human samples and animal models of FJ and knee OA to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridization were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression.”

“Using animal models for spine and knee osteoarthritis, we were able to show that injecting a blocker of miR-181a-5p in knee or facet joints can slow down the process of cartilage destruction. In addition, using this blocker in human cells/tissues of osteoarthritis patients decreases the production of molecules that destroy cartilage.”

The research team led by Dr. Kapoor comprising of Dr. Nakamura (first author of this paper) and other colleagues, is working on evaluating the safety profile of this treatment in order to translate this technology to clinics in the near future.

Dr. Kapoor, who is also with the Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada, told OTW, “Currently osteoarthritis treatment is limited to symptomatic relief with no approved disease modifying therapy available. The miR-181a-5p antisense oligonucleotide that we have tested has shown to protect cartilage from damage during osteoarthritis, suggesting its potential as a disease modifying therapy.”