Research identifies protein that protects healthy joints from osteoarthritis

According to significant new study published in the journal Science Advances, a hitherto unstudied protein in the framework of osteoarthritis may be crucial in the disease's prevention, which featured work by Justin Parreno, an assistant professor at the University of Delaware.

Osteoarthritis is an incurable, painful, and debilitating joint ailment caused by the disintegration of the cartilage that cushions the ends of the bones, known as articular cartilage. It is the most prevalent kind of arthritis, affecting more than 32.5 million Americans, according to the Centers for Disease Control and Prevention. It most commonly arises in the hands, knees, or hips.

Parreno discovered that the protein adseverin helps maintain articular cartilage healthy as a doctorate student at the University of Toronto. This is the first time a particular protein related with cell structure has been identified as being osteoarthritic-protective.

The finding happened virtually by chance. Parreno and his colleagues were working on another cartilage treatment when he discovered that healthy cartilage cells have a lot of adseverin but damaged cartilage cells don't. Adseverin concentration eventually influences the structural scaffolding of cells, known as filamentous(F) actin.

F-actin protects cartilage cells from the pressures that occur when the joints move. Cells eventually perish when they lose F-actin.

"The cells are really round, and you have F-actin around the cells," said Parreno, a member of the University of Delaware's Department of Biological Sciences. "If F-actin is lost, those cells become sensitive due to mechanical stress, and they will most likely die." Dead cells are unable to synthesize the chemicals needed to rebuild cartilage, and the cartilage gradually dissolves."

Not only do the cells die, but the surviving cells begin to generate chemicals that wreak havoc on the cartilage.

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

Current therapies for osteoarthritis either require surgery or focus on pain management. While Parreno acknowledges that the research has not been tested in humans, he believes the discoveries may pave the way for therapies that target the protein.

"If we can maintain the levels of adseverin, or alternatively find a way to keep that F-actin at a high enough level, we might be able to prevent cell death," he added. "We've got to keep these cells alive and healthy."

Through the Delaware Center for Musculoskeletal Research (DCMR), Parreno's group at UD continues to explore the control of F-actin and its link to osteoarthritis processes, including cell death. Tropomyosin, another F-actin-binding protein, is being studied in the lab. According to Parreno, F-actin may be the key to controlling cartilage degradation.

"What I find really groundbreaking about this work is not necessarily the adseverin, but the fact that F-actin is reduced in osteoarthritis and leads to all of these changes," Parreno said. "We know all of these changes are taking place, and if we can figure out what the critical node is in regulating all of these things, we might be able to develop an osteoarthritis therapy." I believe that targeting F-actin might be that, and we have only scratched the surface.

"Adseverin regulates F-actin, but so do other molecules, so we need to know if it is the main molecule or just one of them." Once we know which molecules are critical, we might be able to chemically target them to avoid joint destruction."

It might also be the key to other difficulties in the musculoskeletal system. Parreno is also a member of an interdisciplinary research team that is looking at multi-scale tendon injury and aberrant cellular responses in tendinopathy. Parreno is exploring the role of F-actin in the regulation of tendinosis as part of this work.

Dawn Elliott, Blue and Gold Distinguished Professor of Biomedical Engineering within the College of Engineering and DCMR director, leads the team, which also includes co-investigator Karin Grävare Silbernagel, professor of physical therapy in the College of Health Sciences. The National Institutes of Health awarded the group a nearly $2.3 million, five-year R01 Grant last October.

The study of osteoarthritis is somewhat personal for Parreno. He has been injured as an athlete who grew up playing hockey and now plays basketball and does weights at the Carpenter Sports Building (Little Bob). "I've always been interested in the musculoskeletal system because of sports." Because of this, I believe I was predisposed to orthopedic research. So it's somewhat self-serving. "I know I'm going to get osteoarthritis," he joked.