Osteoarthritis is a painful condition in which the cartilage, the protective cushion between joints, is gradually destroyed. This progressive joint disease affects more than 32 million people in the United States and can eventually cause bone-on-bone friction, joint stiffness, and pain with every movement.
Multiple factors can affect your risk of developing osteoarthritis, including injury, obesity, aging, and genetics. Recent research has found that nearly half of the risk of osteoarthritis is genetic, sparking interest in using genetic data to develop treatments that can halt further deterioration of joint tissue. Masu.
But to develop new treatments, researchers first need to identify genes that directly contribute to the development of osteoarthritis, called “causal” genes. An interdisciplinary research team at the UNC Thurston Arthritis Research Center, consisting of Doug Phanstiel, Ph.D., Richard F. Loeser Jr., M.D., Ph.D., and Brian Diekman, Ph.D., of the UNC School of Medicine, has accomplished just that.
A new study by the same group has identified 13 genes, called “high-probability risk genes,” that directly contribute to joint tissue loss and significantly increase the likelihood of developing osteoarthritis. Their results, published in Cell Genomics, fill a considerable knowledge gap in efforts to define gene targets for therapy.
“Many studies have identified more than 100 ‘risk regions’ in the DNA of osteoarthritis, but few have discovered the causative gene,” said UNC TARC Director Joseph P. Archie Jr. Loser said. Professor at UNC School of Medicine. “If we can identify the causative gene, we can use that information to define new gene targets for the treatment of osteoarthritis.”
Osteoarthritis is the most common form of arthritis. Rheumatologists like Loser often recommend nonsteroidal anti-inflammatory drugs, exercise, and weight loss to help patients with osteoarthritis manage their symptoms. At this time, it is not possible to stop the progression of the disease.
The latest research dates back to 2022, when Phanstiel, Roeser and Diekman received a $2.5 million grant from the National Institute of Arthritis and Musculoskeletal Skin Diseases to further research to develop treatments. The aim was to identify new osteoarthritis risk genes.
The team brought together multiple disciplines to carry out a collaborative research initiative. To build a cellular model of the disease, Loeser’s lab first collected joint tissue from more than 100 human donors. After growing cells in the lab and introducing molecules that induce an osteoarthritis-like condition into the cells, researchers can now study the condition in a living, controlled environment.
Fanstiel, an associate professor in the Department of Cell Biology and Physiology, will leverage the lab’s expertise in genomics and bioinformatics to generate gene expression data and identify genes associated with osteoarthritis risk. Identified by computer. Dr. Brian Diekman, associate professor and gene editing expert in the UNC-NC State Joint School of Biomedical Engineering, will lead a follow-up study to understand what role the causative gene plays in osteoarthritis. did.
Using a genomics approach, they identified 13 genes likely to influence genetic risk for osteoarthritis. Six of the 13 genes are completely new to scientists in terms of their association with joint disease. The newly discovered gene is notable in that it can provide new insight into the range of biological processes that may contribute to osteoarthritis.
“While some of these genes have known roles in osteoarthritis or are involved in processes related to osteoarthritis pathology, the function of other genes remains unknown. It’s not very clear,” said Fanstiel, who is also a member of the UNC Lineberger Comprehensive Cancer Center. “Osteoarthritis risk can be, and is even likely, caused by genetic influences on different processes that operate across different developmental time points and biological conditions.”
Now that these 13 genes have been identified, the research team plans to continue studying them in multiple areas. First and foremost, to identify more genes associated with osteoarthritis, the team is expanding their current study to include a larger donor cohort and samples from multiple cell types.
Researchers are also conducting research to better understand the biological processes triggered by the newly identified causative genes. At the same time, the team is currently conducting drug screening studies to find drug compounds that target biological pathways of interest.
“We hope to discover new treatments that can halt the progression of joint damage at an early stage and prevent the development of the pain and disability experienced by many patients suffering from osteoarthritis,” Professor Loser said.
