A small molecule dubbed kartogenin encourages stem cells to take on the characteristics of cells that make cartilage, a new study shows. Treatment with kartogenin allowed mice with arthritis-like cartilage damage in a knee to regain the ability to use the joint without pain.
The findings where uncovered by molecular biologists at the Genomics Institute of the Novartis Research Foundation in San Diego and provide new clues in the long-running effort to find ways to regenerate cartilage, a central puzzle in the battle against osteoarthritis. Study findings were reported online April 5 in the journal Science.
The new approach taps into mesenchymal stem cells, which naturally reside in cartilage and give rise to cells that make connective tissue. These include chondrocytes, the only cells in the body that manufacture cartilage. Kartogenin steers the stem cells to wake up and take on cartilage-making duties. This is an essential step in cartilage repair that falls behind in people with osteoarthritis, the most common kind of arthritis, which develops from injury or long-term joint use.
The molecular biologists screened 22,000 compounds in cartilage and found that one, kartogenin, induced stem cells to take on the characteristics of chondrocytes. The molecule turned on genes that make cartilage components called aggrecan and collagen II. Tests on mice with cartilage damage similar to osteoarthritis showed that kartogenin injections lowered levels of a protein called cartilage oligomeric matrix protein. People with osteoarthritis have an excess of the protein, which is considered a marker of disease severity. Kartogenin also enabled mice with knee injuries to regain weight-bearing capacity on the joint within 42 days.
Millions of people develop osteoarthritis as they reach old age. Cartilage serves as the shock absorber of the skeleton, but surgery to clean out torn cartilage has limited success, as does surgery to induce growth of a fibrous kind of coating at the ends of bones that have lost their natural cartilage caps. This losing battle leaves bone-on-bone friction, inflammation and pain.
According to Dennis Lox, MD, a sports, physical and regenerative medicine specialist in the Tampa Bay area, until this therapy becomes available to the public, autologous, adipose-derived stem cell therapy is currently available to treat musculoskeletal injuries and conditions, such as osteoarthritis.
Regenerative medicine techniques, such as stem cell therapy and platelet-rich plasma, are growing in use and acceptance, not only among sports professionals, but everyday citizens as well. These regenerative medicine techniques could help musculoskeletal injuries heal more quickly and could possibly help avoid surgery.