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Osteoarthritis: Protein Research May Lead To New Treatments

Osteoarthritis: New Research On Membrane Protein May Yield New Treatments

Date: 20 January 2023

News Source: www.medicalnewstoday.com

New research has shed light on the mechanisms inside the body that can lead to osteoarthritis, and this new data could spur the future development of treatments for the degenerative joint disease and most common form of arthritis. A team of researchers from the United States and Japan released their findings today in the scientific journal Nature.

Existing treatments and therapies for osteoarthritis, such as lifestyle management and joint replacement surgery, focus on managing symptoms after they’ve already become an issue. However, this new research suggests that there’s an underlying cause—a discovery that could lead to the development of new treatments.

Understanding Klotho

Klotho, a type of membrane protein found in the blood circulation and in tissues throughout the body, plays an important role in joint issues. While this mechanism is understood, the underlying reasons for the age-related drop in Klotho levels aren’t as clear.

Researchers said they found evidence suggesting that one reason for the loss of Klotho with aging is the stiffening of the extracellular matrix, the structure that surrounds and gives support to the cells in the body.

“Extracellular matrix stiffening has even been proposed by some to be a common denominator of aging because, like declines in Klotho, stiffening occurs in tissue throughout our bodies as we get older,” explained Dr. Fabrisia Ambrosio, a senior author of the study and the director of the Atlantic Charter Discovery Center for Musculoskeletal Recovery of the Adams Schoen Research Institute at Spaulding, Harvard Medical School.

Making connections

In their research on mice, Ambrosio and her colleagues reported that as this extracellular matrix stiffens, the development of Klotho is repressed.

“Not only does our work suggest that a stiff microenvironment contributes to a loss of Klotho expression, but previous studies have shown that a loss of Klotho also contributes to matrix stiffening,” Ambrosio told Medical News Today. “A vicious cycle therefore ensues." "Opportunities for the development of new therapeutics may involve either strategies to block the mechanical signals from the matrix to the cell that are responsible for inhibiting the gene expression of Klotho and/or strategies to inhibit the pathways that promote matrix stiffening in the first place.”

The researchers also said that age-related cartilage degeneration was observed in male mice, while female mice displayed no appreciable loss of cartilage integrity. This dynamic is different from what’s seen in the human population, where osteoarthritis tends to be more severe in women.

“What we didn’t appreciate at the time is that most aged female mice do not undergo menopause, as do their human counterparts,” said Ambrosio. “Based on these data, we are now very interested in investigating the role of menopause in osteoarthritis in females, as well as the role of menopause in contributing to extracellular matrix stiffening in females.”

While these findings are just one step toward a better understanding of osteoarthritis, experts say they do suggest that there could be ways in the future to intervene before osteoarthritis sets in.

“Opportunities for the development of new therapeutics may involve either strategies to block the mechanical signals from the matrix to the cell that are responsible for inhibiting the gene expression of Klotho, and/or strategies to inhibit the pathways that promote matrix stiffening in the first place,” explained Ambrosio.

Managing osteoarthritis

This research could lead to interventions that stop or inhibit osteoarthritis before it becomes a problem. However, for now, treatment options merely address symptoms rather than modify the disease.

Dr. Kenneth Zaslav is the director of the Center for Regenerative Orthopedic Medicine at Northwell Health in New York and a professor of orthopedic surgery at the Zucker School of Medicine at Hofstra University. He told Medical News Today that a range of injections are available for people with osteoarthritis.

“These are used to treat or mitigate symptoms,” he said. “There’s no evidence, however, that those are disease-modifying. If we couple those with good physical therapy for strength training and flexibility, you can buy a lot of time in treating early osteoarthritis.”

For older adults, joint replacement surgery is an effective way to stop osteoarthritis. But because these replacement joints wear out, surgery isn’t generally an option for younger people. As Zaslav explains, all other forms of treatment, from injections to physical therapy, are designed to treat the condition until surgery is an option.

Injuries such as broken bones or cuts on the skin will heal over time as new cells form. But when an adult breaks their articular cartilage, this isn’t the case.

“It becomes a slow, steady, inexorable wearing away of cartilage around the lesion—the original injury and rubbing on the other surface that ultimately causes arthritis,” Zaslav explained.

For people who have early osteoarthritis, it’s crucial to stay active and avoid carrying too much weight, as every pound gained equals four more pounds of force on the knee. But it’s important to know which activities are safe.

“It’s still OK to cycle, and elliptical, and strength train,” said Zaslav. “But running and cutting sports are going to hasten the wear." Once you’ve torn the meniscus, or torn a ligament, or injured the articular cartilage, the high impact of running is not viable. "Moving to lower impact activities such as cycling, swimming, and strength training instead of running and cutting is one thing you can do.”

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