This may be exactly what has brought some people to their knees.
Joint problems have never been limited to the elderly, as more and more young people suffer from debilitating knee pain and turn to surgical options for relief.
Today, a revolutionary treatment can relieve the inflammation, pain, stiffness and reduced joint mobility that often accompany arthritis or other knee injuries.
Almost everyone will be affected by the wearing away of the protective layer of cartilage at the ends of our bones, either by developing osteoarthritis as we age or due to injuries like ACL tears, where pivoting, jumping and sudden stops are common.
The most common treatment for severe arthritis is surgical replacement of the damaged joint, a costly prevention for a disease that affects millions of people.
However, researchers at Stanford Medicine have discovered a revolutionary treatment in older mice that regrows damaged knee cartilage by restoring naturally lost cartilage and prevents osteoarthritis after knee injury.
New functional joint cartilage was also produced through the treatment, discovered by further studying a protein we naturally produce as we age.
The 15-PGDH protein is described as a gerozyme, or enzyme that becomes more abundant with age and contributes to the progressive loss of tissue function.
Blocking the protein in aged mice was associated with increased muscle mass and endurance, as well as regeneration of bone, nerve and blood cells.
These tissues heal through the multiplication of tissue-specific stem cells and their transformation into specialized cells.
But not cartilage cells. Instead of relying on stem cells, they heal by changing their patterns of genetic activity.
“This is a new way to regenerate adult tissue, and it shows great clinical promise for treating arthritis caused by aging or injury,” lead study author Helen Blau said in a press release.
The gerozyme inhibitor “causes dramatic cartilage regeneration beyond that reported in response to any other drug or intervention,” added the study’s lead author, Nidhi Bhutani.
Previous research by the same team discovered a molecule important for muscle stem cell function, called prostaglandin E2, which 15-PGDH breaks down.
Blocking 15-PGDH allows prostaglandin E2 levels to increase and promote healing of damaged muscle, nerve, bone, liver and blood cells in young mice.
By injecting older mice with a small molecule drug designed to inhibit 15-PGDH, the animals’ knee cartilage became thicker on the joint surface.
Notably, the cells also produced hyaline cartilage, or smooth articular cartilage necessary for healthy joint movement, with Bhutani saying the cartilage regeneration surprised the team and “the effects were remarkable.”
The researchers also looked at whether the inhibitor could help recovery after a traumatic knee injury, as around 50% of people who suffer such an injury go on to develop osteoarthritis.
Mice given the 15-PGDH inhibitor twice a week for four weeks saw a reduced risk of developing arthritis, compared to untreated mice who developed it within four weeks.
Overall, the treatment appears to push the cartilage toward a more youthful biological state without recruiting stem cells.
The researchers also looked at cartilage samples from people with osteoarthritis who were treated with the 15-PGDH inhibitor.
After one week, tissue samples contained less 15-PGDH protein and activity associated with cartilage breakdown decreased, while articular cartilage regenerated.
By observing cellular activity, the team’s perspective on how tissue can heal and regrow was changed.
“It is clear that a large number of cells already existing in cartilage are changing their gene expression patterns,” Bhutani said. “And by targeting these cells for regeneration, we may have the opportunity to have a greater overall clinical impact.”
Although results were limited to mouse models, an oral version of the 15-PGDH inhibitor for age-related muscle weakness exists and has been shown to be safe in humans.
Future clinical trials specifically testing cartilage regeneration will be needed to determine whether the treatment is safe and effective.
Gn Health
