Goodbye joint replacements? Stanford scientists found a way to regrow cartilage and stop arthritis

Scientists have found a way to rejuvenate existing cartilage cells, regrow damaged knee cartilage, and potentially open a path toward treating arthritis without joint replacement.

Scientists have identified a way to restore cartilage in aging knee joints, at least in mice, by blocking a protein whose levels rise with age. The approach not only reversed naturally occurring cartilage loss in older animals, but also protected mice from developing arthritis after knee injuries similar to ACL tears in people.

The findings also showed promise in human tissue. Cartilage samples collected during knee replacement surgeries responded to the treatment by beginning to produce new, functional cartilage.

Together, the results suggest that cartilage damaged by aging or arthritis may be more capable of repair than previously thought. If the strategy ultimately works in people, researchers believe it could potentially lead to an oral medicine or injection that regenerates cartilage and reduces the need for knee or hip replacement surgery.

Osteoarthritis is a degenerative joint disease in which cartilage gradually breaks down, leaving joints painful, swollen and increasingly difficult to move. It affects about one in five adults in the United States and is estimated to account for roughly $65 billion in direct health care costs each year.

Current treatments mainly focus on controlling pain and other symptoms. Once the disease becomes severe, replacing the damaged joint surgically may be the only remaining option. There is currently no drug that can reliably slow or reverse osteoarthritis itself.

The Stanford Medicine-led study instead focused on a protein called 15-PGDH. The researchers have described it as a gerozyme, a term for enzymes that become more abundant with age and contribute to the gradual loss of tissue function.

Previous work by the same group showed that 15-PGDH acts as an important regulator of aging in multiple tissues. Blocking the protein with a small molecule increased muscle mass and endurance in old mice. Doing the opposite, increasing 15-PGDH in young animals, caused their muscles to shrink and weaken. The protein has also been linked to the regeneration of bone, nerve and blood cells.

In many of those tissues, healing depends on tissue-specific stem cells multiplying and developing into specialized cells. Cartilage turned out to behave differently. Instead of relying on stem cells, existing cartilage cells called chondrocytes changed their patterns of gene activity and shifted toward a more youthful state.

"This is a new way of regenerating adult tissue, and it has significant clinical promise for treating arthritis due to aging or injury," said Helen Blau, PhD, professor of microbiology and immunology. "We were looking for stem cells, but they are clearly not involved. It's very exciting."

Blau, who directs the Baxter Laboratory for Stem Cell Biology and is the Donald E. and Delia B. Baxter Foundation Professor, and Nidhi Bhutani, PhD, associate professor of orthopaedic surgery, are the senior authors of the research, which was published in Science. Instructor of orthopedic surgery Mamta Singla, PhD, and former postdoctoral scholar Yu Xin (Will) Wang, PhD, are the lead authors of the study. Wang is now an assistant professor at the Sanford Burnham Institute in San Diego.

"Millions of people suffer from joint pain and swelling as they age," Bhutani said. "It is a huge unmet medical need. Until now, there has been no drug that directly treats the cause of cartilage loss. But this gerozyme inhibitor causes a dramatic regeneration of cartilage beyond that reported in response to any other drug or intervention."