Repair & regeneration of human cartilage damaged by osteoarthritis

Osteoarthritis is one of the leading causes of disability in the US today. The disease occurs when articular cartilage in a joint degenerates. Articular cartilage is the smooth, white tissue that covers the ends of bones where they come together to form joints. It doesn’t regenerate in the same way as other tissue in the body. Articular cartilage allows the bones to glide over each other with very little friction, and it’s essential to movement. As osteoarthritis takes hold, it becomes progressively more painful and difficult to move.

The only way to currently cure osteoarthritis is through joint replacement surgery. It’s not ideal, we don’t have implants available for every joint, and infection is always a risk. Even when a joint replacement is available, it doesn’t last a lifetime. That means young and middle age adults will need to undergo another surgery again later in life.

A treatment that could cure the disease by promoting articular cartilage to heal in the same way as other tissues in the body would give countless patients a less intrusive medical alternative to a joint replacement surgery. Researchers have found a gene, the Phlpp1 (pronounced “flip”) that stops regeneration in cartilage. If we can block the Phlpp action, then cartilage could possibly repair itself. That means there could be a treatment for osteoarthritis other than joint replacement.

Two chemical inhibtors have been found to block Phlpp activity and slow down the progression of osteoarthritis in mice. That’s a great step, but researchers don’t know if that would work in people. The focus of this grant is to test whether or not human articular cartilage can be regenerated when the Phlpp actions are blocked. It’s called the “Phlpp knockout”, and it could be an incredible option for osteoarthritis patients.

This grant will support researchers testing drugs to treat osteoarthritis and support the Phlpp knockout in humans. There are three possibilities that the team will observe. The first is a drug made of tiny molecules that block the gene stopping cartilage from regenerating. The second idea is to find out if it’s possible for adult stem cells to grow into cartilage by blocking the Phlpp activity. Third, this research will look at how controlling Phlpp activity could work on neocartilage, engineered tissue that could replace degenerated articular cartilage.

The researchers working on this grant are the first in the world to identify the Phlpp activity in cartilage regeneration. This is one of the only promising treatments for osteoarthritis being worked on today, and it puts Minnesota at the forefront of cartilage regeneration.

The only way for new osteoarthritis treatments to be developed is through further research funded by this grant. As federal support dries up, grants like this become increasingly more important. Therefore, the advancement of this research, with Regenerative Medicine Minnesota funding, could benefit osteoarthritis patients for generations to come.

Click here to see progress video