They discover how to prevent osteoarthritis or slow its progression

A team of researchers from the University of Delaware (UD) (USA) has identified a protein that may be key to prevent osteoarthritis, a chronic pathology that causes pain and weakness in the joints and is characterized by the breakdown of the cartilage found between the ends of the bones – the articular cartilage – and acts as a shock absorber. Osteoarthritis most commonly affects the hands, knees, or hips and is the most common type of arthritis.

Justin Parreno, an assistant professor at the aforementioned university, discovered that the protein adseverin contributed to maintaining the health of articular cartilage when I was a PhD student at the University of Toronto. It is the first time that a specific protein associated with cell structure has been found to protect against the development of osteoarthritis and the finding came almost by chance when Parreno and his colleagues were working on another cartilage therapy and he discovered that cartilage cells Healthy cartilage cells contain large amounts of adseverin, while unhealthy cartilage cells do not.

The amount of adseverin ultimately regulates the structural scaffolding of cells, called filamentous (F) actin. F-actin acts as a shield against the stresses that occur in cartilage cells when joints move. The loss of F actin causes the cells to eventually die. Not only do the cells die, but the remaining cells begin to produce molecules that cause further problems in the cartilage. The results of his work have been published in the journal Science Advances.

“Dead cells cannot produce the molecules that are required to regenerate cartilage and eventually the cartilage breaks down.”

“The cells are really round and there is F-actin around the cells,” explains Parreno, a member of UD’s Department of Biological Sciences. “If you lose F-actin, those cells are sensitive because they are subjected to mechanical stress and are likely to die. The dead cells cannot produce the molecules required to regenerate cartilage, and eventually the cartilage breaks down.” are producing hypertrophic molecules that result in mineralization and stiffness of the tissues, which leads to a really bad joint,” Parreno said.

Therapy against musculoskeletal problems and tendinopathy

Currently the treatments for arthritis are aimed at controlling pain. Although Parreno has indicated that the research has not been tested in humans, he believes that the findings may open doors to the design of protein-targeted therapies. “If we’re able to keep adseverin levels up or, alternatively, somehow figure out how to keep that F-actin at a high enough level, maybe we can prevent cell death,” he said. “We have to keep these cells alive and healthy.”

Parreno’s lab at UD continues to investigate F-actin regulation as it relates to arthritis processes, including cell death, through the Delaware Center for Musculoskeletal Research (DCMR). The lab is focused on another F-actin-binding protein, called tropomyosin, and Parreno says F-actin may hold the key to regulate cartilage degeneration.

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

“Adseverin regulates F-actin, but so do other molecules, so 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 attack them to prevent joint degradation.”

It may also be the key to others problems in other musculoskeletal tissues. Parreno is also part of an interdisciplinary team investigating tendon damage at multiple scales and rabnormal cellular responses in tendinopathy. As part of this effort, Parreno is investigating the role that F-actin plays in the regulation of tendinosis.

For Parreno, osteoarthritis research is personal as an athlete who played hockey growing up and now plays basketball and lifts weights at the Carpenter Sports Building (Little Bob), so he has found with injuries. “I’ve always been interested in the musculoskeletal system just because of sports. I think I was predisposed to orthopedic research because of that. So it’s partly serving me. I know I’m going to get osteoarthritis,” he says with a smile.


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