28 Jun Pinpointing the Development of Osteoarthritis
An estimated 30 million Americans suffer from osteoarthritis (OA), the leading cause of chronic disability in older adults. Nearly half of all adults over the age of 65 have been affected by the development of osteoarthritis, a degenerative joint disease.
OA creates a painful inflammatory response in the joints, resulting in the breakdown of cartilage and damage to surrounding tissues. As OA progresses, it destroys cartilage, the layer of elastic tissue that cushions the ends of bones at the joints. Without this important buffer, bones often become damaged. Over time, OA typically worsens, (especially if left untreated), leading to agonizing pain, swelling, stiffness and loss of mobility.
With funding from the Arthritis National Research Foundation (ANRF), Tao Yang, PhD, an assistant professor and bone disease expert at the Van Andel Research Institute, is investigating the complex web of biochemical cues that regulate skeletal health, including the development of osteoarthritis. In 2017, Dr. Yang was named ANRF’s Frances D. Morongo Memorial Fellow and he was recently awarded a second year of funding for 2018-19.
“We are laying a foundation for future research that will advance our efforts to develop new therapies for osteoarthritis,” says Dr. Yang, whose laboratory studies mechanisms that regulate skeletal physiology and disease development. “Given the prevalence of osteoarthritis and the debilitating effects that it can have, new strategies for treating OA are becoming increasingly urgent, particularly as current treatments for OA are very limited.”
As the global population continues to grow and age, how can Dr. Yang pinpoint specific mutations that drive the development of osteoarthritis?
Multiple factors contribute to the development of osteoarthritis and the loss of cartilage, including aging, injury and a genetic predisposition. Aging thins joint cartilage, stretches ligaments and weakens bones. Destructive signaling molecules spur wayward inflammatory responses that destroy joints. An additional culprit in the aging process is the exhaustion of stem cells that normally give rise to healthy bones.
A specific mutation in a human protein, first identified in Europe, dramatically raises the risk of OA. Researchers found a decrease in a vital enzyme in patients with osteoarthritis.
“Our idea is that this pathway is so important to maintaining the integrity of the joints that we are looking for ways to enhance its activity or availability to delay the development of OA,” says Dr. Yang.
Thanks to the grants from the Arthritis National Research Foundation, Dr. Yang and his team are continuing to investigate these biochemical pathways using their recently developed, unique model of the disease, which allows them to study OA in a controlled way. “We found that mice without this enzyme aged more quickly,” says Dr. Yang. “We are exploring whether we can protect against osteoarthritis caused by aging or injury by increasing its activity in the cells of the joints.”
In the human body, both bone and cartilage arise from particular stem cells or progenitor cells that also play important roles in skeletal growth and repair. We recently found that a mechanism responsible for protein “tagging” and “de-tagging” can influence the functions and levels of aging-related proteins in skeletal progenitor cells. A disruption of such mechanism in mice results in premature aging in the skeletal system.
Dr. Yang believes his work will one day lead to new ways to slow or reverse human disease. “Using our animal model, we hope to find ways to enhance the effect of this important enzyme in the joints,” he says. “I continue to be inspired by my grandfather, whose OA caused him enormous pain and made him give up his favorite sports. His health then worsened due to his lack of exercise. I realized that osteoarthritis, which is seemingly a disease of the joints, can cause a chain reaction that broadly affects a person’s life style and their overall health.”
Musculoskeletal diseases are among the most common medical problems worldwide. Since OA is a progressive disease, bone degradation inevitably leads to disabling pain and loss of mobility. Researchers in Dr. Yang’s lab are exploring ways to disrupt the degenerative process and improve skeletal health. Thanks to the discovery of this key enzyme, Dr. Yang’s research is bringing hope for a new way to help people prevent bone deterioration and joint damage.