This story started with a dozen male research mice survivors from hurricane Sandy in 2012. The storm devastated Dr. Bruce Cronstein’s research lab, but born from the destruction was Dr. Cronstein’s 5-year Arthritis Foundation Investigator-funded project, “The Role of Adenosine Receptors in Osteoarthritis.”
He described the damage: “Our labs were closed for nearly a year and a half. We lost a lot of our animal facilities. However, once a lot of the debris was cleared, we were able to go in and found that some of our mice had survived.”
Dr. Cronstein and his team discovered that the rescued mice could no longer breed, and they had difficulty moving and holding food. This was unexpected. To look for answers, the team took CT scans of the mice’s knees and saw the mice had osteoarthritis (OA). “We had been looking at adenosine receptors in cells because they are known to be involved in anti-inflammatory processes. The mice we rescued were lacking an adenosine receptor,” Dr. Cronstein explained. “We hadn’t been looking at OA, but we thought there might be a link. So we started to try to find out how the adenosine receptors were involved with OA.”
Adenosine, a sugar-based molecule in the body, is involved in energy use in cells (in the form of ATP) and, because it contains sugar, can be used as a source of food for cells. Adenosine receptors detect changes in the amount of adenosine present in or around a cell. They can stimulate or inhibit different cell reactions.
Dr. Cronstein explained, “With the mice, we studied their chondrocytes, the cells that become cartilage. If we removed the adenosine receptors in these cells, the chondrocytes behaved as if they have OA.”
What does that mean for humans? Do human cells react the same way? According to Dr. Cronstein, human cells lacking adenosine receptors act differently. “What we found is that the chondrocytes in OA patients are pre-maturely aged,” Dr. Cronstein continued. “They don’t make as much ATP, so they don’t release as much adenosine. Adenosine acts as a food for cells and as an anti-damage molecule. When there is not enough adenosine, cells age pre-maturely.”
Based on these observations, Dr. Cronstein and his team began looking at adenosine and its effects in OA in rats. The team began injecting adenosine into injured joints. It seemed to be working. But because cells use adenosine as food, it didn’t last long in the joint. “We need to develop a longer-lasting form of adenosine,” said Dr. Cronstein.
“What we are seeing is that our model is very consistent with current understanding of aging and aging chondrocytes. People develop OA from aging and from injuries,” explained Dr. Cronstein. “In 5 years, we hope to have an injectable form of adenosine that will last. We hope to be able to do clinical trials in humans within 5 to 8 years.”
According to Dr. Virginia Kraus, a rheumatologist and professor of medicine, pathology, and orthopedic surgery at Duke University School of Medicine in North Carolina, “This study highlights new insights into the molecular causes of OA that are leading to new ways to treat this debilitating disease. The proposed treatment with adenosine is particularly attractive as it has beneficial effects on bone and cartilage so could be a treatment for the whole joint.”
Dr. Cronstein is a professor and Director of Collaborative Research at the NYU School of Medicine. He and his team have recently published the results of this study, entitled “Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression,” in the May 11,2017 online publication Nature Communications.