Goodbye to Joint Replacement? Scientists Find a Way to Regenerate Cartilage and Combat Arthritis

Stanford University researchers, by inhibiting a protein that increases with age, regenerated lost knee cartilage in aging mice and reduced the likelihood of arthritis following knee injury. The promising response of human cartilage samples has raised the question of whether damaged cartilage could one day be repaired without joint replacement.

According to Ambassador Arjan's report, quoted by sciencedaily, Stanford University researchers have identified a method that can restore cartilage cells to a younger state by inhibiting a protein associated with aging and help rebuild damaged knee cartilage. This method has had remarkable results in old mice, and signs of tissue regeneration have been observed in human cartilage samples; A finding that can provide a new way to treat arthritis and reduce the need for joint replacement in the future.

Scientists have found a way to regenerate damaged knee cartilage that focuses on inhibiting a protein called 15-PGDH; A protein whose amount increases with age and plays a role in reducing tissue function.

By inhibiting this protein, researchers were able to restore the lost knee cartilage of old mice to a large extent. This method also reduced the possibility of arthritis in mice that suffered injuries similar to anterior cruciate ligament tears.

The test results on human cartilage samples were also promising. The samples that were removed from patients with arthritis and during total knee joint replacement surgery, after exposure to this protein inhibitor, showed signs of producing new and functional joint cartilage.

These findings suggest that cartilage damaged by aging or arthritis may have a greater regenerative capacity than previously thought. However, it is not yet clear whether this method can effectively regenerate cartilage in the human body or reduce the need for knee and hip replacement surgery.

Targeting the cartilage destruction factor in arthritis

Arthritis is a degenerative joint disease in which the cartilage is gradually destroyed. As this protective tissue becomes thinner, it becomes more difficult for the bones to move over each other, and pain, swelling, and movement limitation increase.

It affects about one in five adults in the United States, and direct health care costs are estimated at $65 billion annually.

Current treatments mainly focus on controlling pain and other symptoms. In advanced stages of the disease, joint replacement surgery may be the only option left. Currently, there is no drug available that can reliably stop or reverse the main process of cartilage destruction in osteoarthritis.

In this study, instead of focusing on symptom relief, Stanford University researchers investigated a protein called 15-PGDH. They place this protein in a group of enzymes that increase with age and help to gradually reduce the function of body tissues. Researchers have given the term "Gerozyme" to this group of enzymes.

Previous studies of the same group have shown that 15-PGDH plays a role in aging-related processes in different tissues. Inhibition of this protein using a small molecule increased muscle mass and improved endurance in old mice. On the contrary, increasing the activity of this protein in young mice led to shrinking and weakening of their muscles.

This protein is also related to bone, nerve and blood cell regeneration processes.

In many tissues of the body, repair is done with the help of specialized stem cells; Cells that multiply and become specialized cells. But the cartilage showed a different behavior.

In this tissue, it seems that the existing cartilage cells, called chondrocytes, change the activity pattern of their genes and return to a younger biological state without the need for stem cells.

Helen Blue, professor of microbiology and immunology at Stanford University, said: "This is a new method of regenerating mature tissue and has significant clinical potential for the treatment of osteoarthritis caused by aging or injury. We looked for stem cells, but it turned out that these cells do not play a role in the regeneration process. This is very exciting."

Blue is the director of the Baxter Stem Cell Biology Laboratory at Stanford University. He and Nidi Butani, associate professor of orthopedic surgery, are the senior researchers of this study. The results of this research have been published in the scientific journal "Science".

Significant regeneration of cartilage in aged mice

Pointing to the need for extensive treatment in this area, Nidi Butani said that millions of people suffer from joint pain and swelling as they age, and so far, a drug that directly targets the main cause of cartilage loss has not been available.

According to him, the inhibitor of this germoenzyme has been able to create a significant regeneration in the cartilage; An effect that, according to the researchers, exceeded the results reported for many other drugs and interventions.

There are different types of cartilage in the human body, each of which has a different function. Elastic cartilage is a soft and flexible tissue that is present in structures such as the external ear. Fibrocartilage is stronger and helps bear force in areas such as the intervertebral discs.

The third type is hyaline cartilage; Smooth and slippery tissue that allows bones to move over each other with little friction. Articular cartilage is of the same type and is present in joints such as knees, hips, shoulders and ankles.

Articular cartilage is one of the most important tissues that are damaged by arthritis.

Aging, joint injuries and obesity can play a role in the occurrence or progression of this disease. During osteoarthritis, chondrocytes begin to produce inflammatory molecules and simultaneously break down collagen. Collagen is a structural protein that provides an important part of cartilage strength.

As collagen decreases, cartilage becomes thinner and softer. Inflammation also aggravates the pain and swelling and finally, the normal movement of the joint is disturbed.

One of the main challenges of treating arthritis is that articular cartilage naturally has a limited ability to repair itself. Although researchers have identified stem or progenitor cells capable of forming cartilage in bone, so far they have not been successful in identifying a similar population of cells in articular cartilage itself.

How was the aging-related protein targeted?

The previous researches of the Blue laboratory showed that a molecule called prostaglandin E2 is important in the function of muscle stem cells. 15-PGDH protein breaks down this molecule.

Inhibiting 15-PGDH or increasing the level of prostaglandin E2 was previously associated with improved regeneration of muscles, nerves, bones, colon, liver and blood cells in mice.

These findings led the researchers to question whether this same biological pathway can also play a role in the destruction of cartilage caused by aging or injury.

To investigate this issue, the amount of 15-PGDH protein in the knee cartilage of young and old mice was compared. The results showed that the amount of this protein almost doubles with age.

The aged mice were then given a drug containing a small molecule designed to inhibit 15-PGDH. In one experiment, the drug was injected into the abdominal cavity to work throughout the body. In another experiment, the drug was injected directly into the knee joint.

Both methods had significant results.

Before treatment, the knee cartilage of old mice was thinner and less functional compared to young mice. But after the treatment, the thickness of the cartilage at the joint surface increased.

The important point was that the regenerated tissue was of hyaline cartilage type; The same type of smooth, specialized cartilage that is essential for healthy joint movement, not fibrous cartilage that has different mechanical properties.

Butani said that cartilage regeneration to this extent in old mice was unexpected, even for the researchers themselves.

Reducing the possibility of arthritis after cruciate ligament injury

The researchers also investigated whether inhibiting 15-PGDH could prevent osteoarthritis after severe knee injuries.

Anterior cruciate ligament or ACL tear is one of the most common injuries in sports such as football, basketball and skiing; Sports in which sudden changes in movement direction, quick stops and jumps put a lot of pressure on the knee.

Surgery can repair the damaged ligament, but treating the initial injury does not necessarily prevent long-term joint destruction. Estimates cited in this research show that about 50% of people who experience such an injury will develop arthritis in the affected joint within about 15 years.

In animal experiments, researchers gave 15-PGDH inhibitor to mice twice a week for four weeks after causing damage.