A new report published in Nature Communications shows that having adenosine, which is a biochemical, plays a role in making and sustaining cartilage. This finding may reveal potential treatments for most common joint diseases.
The molecule adenosine is derived from adenosine triphosphate (ATP), which plays a role in inflammation and diminishes with age. The result is less natural adenosine in the body to make and sustain cartilage. Until now, scientists had not linked diminished adenosine levels to osteoarthritis, the commonplace, “wear-and-tear” form of arthritis.
Researchers used rats with damage to the anterior cruciate ligament (ACL), which is known to lead to osteoarthritis in humans. They found that maintaining high levels of adenosine in the rats, prevented them from developing disease. If their findings translate to trials in humans, the researchers from NYU Langone Medical Center say adenosine replacement therapy could potentially delay the onset of osteoarthritis and the need for joint replacements.
“We found that if adenosine levels decrease, or if the capacity to respond to adenosine diminishes, cartilage starts to degenerate,” says study senior investigator Bruce Cronstein, MD, the Dr. Paul R. Esserman Professor of Medicine at NYU Langone. “Our study suggests that diminished ATP and adenosine production are likely contributing factors to the development of osteoarthritis in aging individuals,” says Cronstein, who also serves as the director of the Clinical and Translational Science Institute (CTSI), and chief of the Division of Translational Medicine at NYU Langone.
The study suggests that greater risk for osteoarthritis may be driven not by lower adenosine levels alone. Instead, they believe lower levels of the protein on the surface of chondrocytes designed to receive and pass on adenosine’s signal, are in play.
Adenosine helps to sustain such cells by fitting into a protein called the A2A adenosine receptor on their surfaces, like a key into a lock. And, the researchers found that the mice lacking the A2A adenosine receptor did not walk as easily or as well as mice with the A2A receptor. Radiologic examination of the knees of mice without the A2A receptor confirmed that they had osteoarthritis.
When they administered adenosine packaged in lipid bubbles into rats’ ACL injuries, Cronstein and team found that the excess adenosine prevented the development of osteoarthritis in the animals.
“Because joints may have to be replaced again and again, if we can put off the need for joint replacement until later in life, odds are that patients will only have to have this done once,” says Cronstein.