Classic Pac-Man video game helps explain nationally recognized arthritis research

Two University of Calgary scientists are being recognized for their innovations supporting the treatment of osteoarthritis, a common and debilitating swelling of the joints affecting millions worldwide.

Arthritis Society Canada named Cumming School of Medicine researchers Dr. Antoine Dufour, PhD, and Dr. Roman Krawetz, PhD, among the recipients of the national charity’s Top 10 Research Advances of 2023 award. 

The scientists led a team of researchers in a study of how the enzyme Tryptase β disrupts natural anti-inflammatory and joint lubricating activities, contributing to the onset of osteoarthritis. The research was published in Nature Communications last year.

The Pac-Man analogy

Dufour and Krawetz use a Pac-Man analogy to help decode the complex science of arthritis.

Their quest centres around the relationship between the enzyme Tryptase β, which is a protease or molecular scissor that disrupts the effectiveness of a lubricating protein in the joint, known as PRG4 or lubricin. When PRG4 is cut by Tryptase β, the result is increasing inflammation and damage to the joint. Blocking the lubricating protein can lead to osteoarthritis. 

“Tryptase β acts like the character Pac-Man in the classic video game, consuming PRG4/lubricin which is represented by the dots in the game. This leads to an increase in inflammation,” says Dufour, principal investigator of the study. 

Protease inhibitors are substances that usually help to slow down or prevent the activity of enzymes like Tryptase β, so they represent the ghosts in the video game. In the case of osteoarthritis, these inhibitors can’t fully halt the ‘Pac-Man’ enzymes, which can result in continued damage to a joint.

“Our research is focused on better understanding these processes and finding ways to control them, to mitigate long-term damage and alleviate pain for those living with osteoarthritis,” says Dufour.

Dufour and Krawetz, in their pursuit to better understand what’s causing the decrease of the protein PRG4, sought to identify how to reduce the impact of Tryptase β on joint inflammation.

“A better understanding of the interactions between Tryptase β and PRG4, particularly after an injury, could spawn new ways to combat osteoarthritis,” says Krawetz.

Advancing to the next level

For example, researchers are continuing to study the complex interactions between the enzyme Tryptase β and a lubricating protein PRG4 to observe how to best maintain joint lubrication and avoid the symptoms of osteoarthritis. They are now studying how administering a drug to the affected joint may inhibit the negative effects of Tryptase β, accompanied by an injection of a laboratory-produced form of PRG4 to reinforce its protective qualities. 

Arthritis Society Canada is also funding this research that seeks to eventually develop a Tryptase β inhibitor.