On Fridays, we often write about getting outside or exercising. If you have arthritis, you may see those blogs and write them off as not for you. However, new research may be opening up future treatments for arthritis.
Researchers at Stanford found that blocking an aging protein in mice regrew cartilage and reduced arthritis in mice. It also helped injured mice recover more quickly and avoid developing arthritis. The team used the same approach in a lab to grow functional human cartilage.
The 15-PGDH protein becomes more common as we age and seems to cause tissue health to decline. Older research from the same lab found that it was linked to the breakdown of muscles, nerves, bones, organs and blood cells. They found that blocking it allowed the body to repair itself.
Cartilage isn’t good at repairing itself, even in young people. "Once collagen and other cartilage-building molecules fall, the tissue thins and softens. Pain and swelling often follow. Researchers have tried many repair strategies, including transplanted cells and scaffolds. But reliably restoring articular cartilage has remained difficult," said Dr. Mamta Singla of Stanford.
Instead of looking for a way to repair cartilage, they studied whether 15-PGDH was elevated in cartilage as mice aged. It was two times higher in older mice than in younger. When they blocked the protein, they were surprised by how well the cartilage repaired itself.
For the human component of their experiment, the team used cartilage taken from people with arthritis who were having a knee replaced. When treated with the protein inhibitor for a week, the cartilage matrix was reforming and its mechanical stiffness was improving, so it would be able to handle more stress during movement.
“Phase 1 clinical trials of [an oral] 15-PGDH inhibitor for muscle weakness have shown that it is safe and active in healthy volunteers,” said Stanford’s Prof. Helen Blau. “Our hope is that a similar trial will be launched soon to test its effect in cartilage regeneration. We are very excited about this potential breakthrough. Imagine regrowing existing cartilage and avoiding joint replacement.”
“This is a new way of regenerating adult tissue, and it has significant clinical promise for treating arthritis due to aging or injury,” said Prof. Blau. “We were looking for stem cells, but they are clearly not involved. It’s very exciting.”
