Nearly 27 million Americans suffer the joint-damaging ravages of osteoarthritis (OA), the most common type of degenerative joint disease. Patients with OA experience a gradual destruction to the layer of bone-cushioning cartilage that provides a smooth gliding surface for the joints.
As the disease progresses, fluid leaks into the lining of the joints and disrupts the formation of new healthy cartilage. Damaged cells begin to form painful bony spurs as errant cells multiply and grow haphazardly. As cartilage breaks down further, the grinding of bone-on-bone causes pain, swelling, bone deformities and loss of motion.
“Cartilage diseases, particularly OA, are one of the leading cause of disability, severely affecting quality of life,” says Wentian Yang, MD, PhD, Associate Professor of Medicine and Associate Professor of Orthopaedics at Brown University. “Current treatments focus on symptom relief, but don’t significantly alter the joint-destroying progression of the disease.”
Research has shown that osteoarthritis results from a destructive cellular process, not just mechanical wear and tear. Because of cartilage’s very limited ability to self-heal, total joint replacement surgery remains the only option for the painful and debilitating disease.
Articular cartilage is the smooth, white tissue that covers the ends of bones where they come together to form joints. Working with transgenic mice, Dr. Yang first identified a novel population of progenitor cells that are capable of migrating toward articular cartilage during development. “By manipulating cells in a controlled manner, we are working to identify molecular pathways in cartilage regeneration. We want to learn what’s happening inside the cell.”
Dr. Yang is investigating genetic signaling and enzyme regulation in the development of cartilage using genetically modified mice. Working with a novel pool of stem cells, he is trying to find out whether a specific enzyme, SHP2, modulates the growth of cartilage by these cells.
In the lab, Dr. Yang is testing the hypothesis that loss of SHP2 can promote stem cell production, leading to rebuilding of cartilage in the joints. If he can identify the molecular mechanisms involved, it will catalyze the development of novel therapeutics to treat OA and other degenerative cartilage diseases.
Thanks to his ANRF-funded research, Dr. Yang has received his first round of funding from the National Institutes of Health. “I am sincerely honored and very grateful to receive the Ethelmae Haldan Grant for Innovative Science in Osteoarthritis from ANRF,” he says. “My goal is to conduct top-flight musculoskeletal research with the aim of improving patient care and outcomes. I am confident that every step we move forward in OA research eventually will lead to a cure.”