Protein Protects Healthy Joints From Osteoarthritis

According to ground-breaking new research, which included work by Justin Parreno, an assistant professor at the University of Delaware, a hitherto unstudied protein in the framework of osteoarthritis may be crucial in the disease’s prevention.

Osteoarthritis is a chronic, painful, and disabling disorder of the joints characterized by the disintegration of the articular cartilage, the tissue that protects the ends of the bones. According to the Centers for Disease Control and Prevention, it affects more than 32.5 million Americans and most frequently affects the hands, knees, or hips.

When Parreno discovered that the protein known as adseverin aids in maintaining the health of the articular cartilage, he was a doctorate student at the University of Toronto. It has never before been proven that a particular protein connected to cell structure can prevent osteoarthritis.

The finding almost happened by mistake. When Parreno discovered that good cartilage cells contain significant levels of adseverin whereas unhealthy cartilage cells do not, he and his colleagues were working on another cartilage therapeutic. Adseverin concentration ultimately controls filamentous(F) actin, the structural framework of cells.

When the joints move, f-actin protects cartilage cells from the pressures that result. Cells that lose F-actin eventually perish.

“The cells are really round, and you have F-actin around the cells,” said Parreno, a member of UD’s Department of Biological Sciences. “If you lose F-actin, those cells are sensitive because there is mechanical stress on them, and they will probably undergo death. Dead cells aren’t able to produce the molecules that are required to regenerate cartilage, and eventually the cartilage degrades.”

In addition to the cells dying, the remaining cells begin to release substances that worsen the cartilage’s issues.

“The cells that remain are also producing hypertrophic molecules resulting in mineralization and tissue stiffness which leads to a really bad joint,” Parreno said.

Surgery or pain management are the two main current treatments for osteoarthritis. Despite the fact that the research has not been tested on humans, Parreno said the results may pave the way for therapies that target the protein.

“If we’re able to maintain the levels of adseverin, or alternatively somehow figure out how to keep that F-actin at a high enough level, perhaps we can prevent cell death,” he said. “We’ve got to keep these cells alive and healthy.”

Through the Delaware Center for Musculoskeletal Research (DCMR), Parreno’s lab at UD is still looking into how F-actin regulation relates to osteoarthritis processes, including cell death. Tropomyosin is a different F-actin-binding protein that is the focus of the lab. F-actin, according to Parreno, might be the key to controlling cartilage deterioration.

“What I really find groundbreaking about this work is not necessarily adseverin, but that F-actin is reduced in osteoarthritis and leads to all of these changes,” Parreno said. “We know all of these changes are happening and if we can find out what’s the critical node in regulating all of these things, then we may be able to develop an osteoarthritis therapy. I think targeting F-actin might be that and we have just uncovered the tip of the iceberg.

“Adseverin regulates F-actin, but so do other molecules, so that’s why we need to understand if it is the main molecule, or if it is just one of them. Once we figure out which molecules are important perhaps we can chemically target them to prevent joint degradation.”

It might possibly hold the solution to various disorders with different musculoskeletal tissues. Parreno is also a member of an interdisciplinary group looking at tendinopathy’s multi-scale tendon injury and aberrant cellular responses. In support of this, Parreno is looking into how tendinosis is controlled by F-actin.

Dawn Elliott, a Blue and Gold Distinguished Professor of Biomedical Engineering in the College of Engineering and the director of the DCMR, serves as the team’s lead investigator. Karin Grävare Silbernagel, a professor of physical therapy in the College of Health Sciences, serves as the team’s secondary investigator. The National Institutes of Health awarded the team a five-year, roughly $2.3 million R01 Grant last October.

The study of osteoarthritis is somewhat personal to Parreno. He has had injuries as a hockey player who now plays basketball and exercises weights at the Carpenter Sports Building (Little Bob). “Sports have always piqued my interest in the musculoskeletal system. I believe this predisposed me to a career in orthopedic research. So I’m sort of helping myself. I’m going to develop osteoarthritis, he remarked, grinning.

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