Scientists have found a drug that can interrupt the body’s response to injury.
Osteoarthritis affects 240 million people worldwide and is one of the most common causes of disability.
Currently, no therapeutics exist to prevent this disease, but recent research reveals that the application of a proprietary peptide known as SS-31 may protect cartilage from the injury that leads to arthritis.
While the prevalence of osteoarthritis continues to rise, current drugs target only the symptoms, not the underlying disease itself.
Lead author Dr Michelle Delco says progress on osteoarthritis treatment has been slow going.
“Forget preventing osteoarthritis,” she said, “right now we don’t have a single drug that even slows down progression of the disease.”
In younger individuals and athletes, arthritis typically develops following joint trauma. But how injury to the cartilage surface is translated into an ongoing degenerative process has been unclear.
Dr Delco believes mitochondria, the ‘battery pack’ of the cell, are key mediators of this injury-to-disease cascade, but there was no direct evidence for that role.
Now, Dr Delco and her colleagues in biomedical engineering and physics have found that mitochondria are a linchpin in the body’s response to injury. They’ve also found a drug that can interrupt the injury response.
That drug, SS-31, was developed by Dr Hazel Szeto a co-author of the paper. SS-31 is known to protect and heal mitochondria in other parts of the body.
Dr Delco and her colleagues were the first to explore its effects in cartilage, and revealed in an earlier study that SS-31 helped protect injured chondrocytes (the cells found in otherwise healthy cartilage) days after an injury.
Dr Delco wanted to further understand how mitochondria respond to injury, and how SS-31 might protect cells.
“Since osteoarthritis is caused by both biological and mechanical factors,” she said, “we need to evaluate them simultaneously to understand what is happening during injury.”
To do this, the team developed a novel experimental setup, one that allowed them to observe and compare huge numbers of cartilage cells and their mitochondria during and immediately after injury.
“Typically, to study mitochondria, researchers crush up the tissue and isolate the cells or individual mitochondria,” Dr Delco said.
“But to study the effects of tissue injury, we needed to monitor mitochondrial function in cells within the dense cartilage matrix during a rapid impact. We also had to track the fate of thousands of individual cells over time.”
To do this the team used a device that delivered a single, high-speed impact to cartilage samples.
To visualise the physiological effect of injury on cells and their mitochondria, the team used special dyes that indicate if mitochondria are healthy or dysfunctional, and if cells are alive or dead.
Using their newly developed injury-imaging system, the experiment yielded insights into the fate of individual cells during impact.
“We discovered that in control samples, mitochondrial dysfunction is immediate after injury,” Dr Delco said.
“The organelles are responding to the mechanical forces of the impact. They become depolarised – like a discharged battery, they can no longer drive energy production. They also become swollen and lose their tightly folded inner membrane structure.”
In contrast, the mitochondria in SS-31-treated cartilage maintained their normal, healthy form; dramatically fewer cells died compared with the control samples.
“Treated samples looked very similar to those that hadn’t been injured at all,” Dr Delco said.
While SS-31’s mechanism of action is not completely known, scientists do know that the peptide enables mitochondria to maintain membrane structure and function during various types of cellular injury – referred to as ‘mitoprotection’.
“Our finding that SS-31 has this protective effect after mechanical injury is exciting,” says Dr Delco. “It suggests mitoprotection may be a new strategy for preventing arthritis after joint trauma.”
Do you suffer from osteoarthritis? Are you hopeful this treatment may provide a solution soon?
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