According to the new research published in the journal Science Advances has identified a previously unstudied protein that may hold the key to preventing osteoarthritis, a painful and debilitating joint condition. Led by assistant professor Justin Parreno from the University of Delaware, the study sheds light on the role of adseverin, a protein associated with cell structure, in maintaining the health of articular cartilage.
Osteoarthritis is characterized by the breakdown of this cartilage and impacts over 32.5 million Americans, making it the most common type of arthritis. Parreno’s journey began during his time as a doctoral student at the University of Toronto. While working on another cartilage therapy, he stumbled upon the significance of adseverin.
Healthy cartilage cells contained substantial amounts of this protein, while unhealthy cells did not. Adseverin was found to regulate the structural scaffolding of cells known as filamentous (F) actin. F-actin acts as a protective shield against stresses on cartilage cells caused by joint movement. The loss of F-actin leads to cell death.
Parreno explains, “If you lose F-actin, those cells are sensitive because there is mechanical stress on them, and they will probably undergo death. Dead cells can’t produce the molecules that are required to regenerate cartilage, and eventually, the cartilage degrades. The repercussions of cell death extend beyond mere mortality. The remaining cells produce hypertrophic molecules that contribute to mineralization and tissue stiffness, exacerbating the joint’s deterioration.
Current treatments for osteoarthritis primarily focus on pain management or surgical intervention. Parreno acknowledges that the findings, while not yet tested in humans, could pave the way for targeted therapeutics centered around adseverin. He states, “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. We’ve got to keep these cells alive and healthy.”
Parreno’s ongoing research at the University of Delaware’s lab delves further into the regulation of F-actin’s role in osteoarthritis, particularly cell death. This work is conducted through the Delaware Center for Musculoskeletal Research (DCMR). Parreno and his team are also exploring the impact of another F-actin-binding protein, tropomyosin, to uncover strategies for regulating cartilage degeneration.
While adseverin’s significance is noteworthy, Parreno highlights the broader implications of F-actin’s involvement in osteoarthritis processes. He underscores that understanding the critical node in regulating these processes could pave the way for osteoarthritis therapies. Parreno believes F-actin might hold this key, and the research has only scratched the surface.
He notes, “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.” Interestingly, this research could extend beyond osteoarthritis.
Parreno collaborates with an interdisciplinary team investigating multi-scale tendon damage and cellular responses in tendinopathy. He’s exploring how F-actin plays a role in regulating tendinosis, a condition involving the degeneration of tendons. The research team, led by primary investigator Dawn Elliott, a distinguished professor of biomedical engineering, is also composed of Karin Grävare Silbernagel, a professor of physical therapy.
The group received a significant grant from the National Institutes of Health to advance their research in this area. For Parreno, this research hits close to home. A former athlete who continues to engage in physical activities, he understands the musculoskeletal system’s importance through his personal experiences. Parreno’s passion for orthopedic research stems from his own predisposition to sports-related injuries. He concludes with a smile, “I know I’m going to get osteoarthritis.”