A big step in repairing damaged cartilage could impact OA treatments

In what could be a major breakthrough for patients with osteoarthritis (OA), researchers found that by blocking a compound commonly found in damaged, aging cartilage, the cartilage can be triggered to regrow.The finding could lead to treatments designed to reverse age-related cartilage damage and were published by researchers from Stanford University in Science. OA affects one out of five adults and is a chronic degenerative disease. One challenge has been that “cartilage has low regenerative potential, which makes repair of damage difficult even in healthy young patients. This difficulty is exacerbated with aging,” the authors wrote. OA sees damage in hyaline cartilage, also called articular cartilage. As joints age or respond to injury, inflammatory molecules gradually break down collagen, the key structural component of cartilage.Various OA studies tried tissue engineering approaches using stem cells or chondrocytes but didn’t manage to get the needed results for cartilage regeneration. The team tried a different tact and looked at the role of 15-hydroxy prostaglandin dehydrogenase (15-PGDH). This prostoaglandin-degrading enzyme is elevated in the articular cartilage of aged or injured mice—but occurs in significantly lower levels in young mice with non-injured cartilage. The researchers refer to 15-PGDH as a ‘gerozyme inhibitor’ since it is associated with aging. The term describes “a class of dysregulated enzymes that accelerate tissue aging to describe the role of 15-PGDH in aging,” the authors wrote. Earlier studies demonstrated that when 15-PGDH was inhibited, damaged muscle, nerve, bone, colon, liver and blood tissues regenerated more effectively in young mice. But what would happen if 15-PGDH were inhibited in live mice in OA models? A series of studies were conducted using both young and old mice, with and without OA. Some were injected with a compound that inhibited 15-PGDH while others were given placebo. Some mice were given injections into the abdomen, while others got injections directly into the knee joint.In the end, it was found that mice with injured cartilage and were treated with 5-PGDH inhibition showed cartilage regrowth and protection from OA, while those that got placebo continued to have degeneration. Indeed, “15-PGDH inhibition alters the cartilage composition to resemble a younger cartilage,” they wrote.Further laboratory studies were conducted in samples of human tissue from OA patients. These too showed 15-PGDH inhibition lead to signs of regeneration.Thus far, it appears the gerozyme inhibitor is safe in humans. At least according to phase-1 studies that were conducted using a 15-PGDH inhibitor for muscle weakness, according to a Standford University press release.

A big step in repairing damaged cartilage could impact OA treatments

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