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.
Targeting the damage behind osteoarthritis 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.
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