Hopkins scientists have turned their view of osteoarthritis inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, they now have evidence that the bone underneath the cartilage is also a key player and exacerbates the damage. In a proof-of-concept experiment, they found that blocking the action of a critical bone regulation protein [TGF-beta 1] in mice halts progression of the disease.
The prevailing theory on the development of OA focuses on joint cartilage, suggesting that unstable mechanical pressure on the joints leads to more and more harm to the cartilage—and pain to the patient—until the only treatment option left is total knee or hip replacement. The new theory, reported May 19 in Nature Medicine, suggests that initial harm to the cartilage causes the bone underneath it to behave improperly by building surplus bone. The extra bone stretches the cartilage above and speeds its decline.
“If there is something wrong with the leg of your chair and you try to fix it by replacing the cushion, you haven’t solved the problem,” says Xu Cao, director of the Center for Musculoskeletal Research in the Department of Orthopaedic Surgery. “We think that the problem in OA is not just the cartilage ‘cushion’ but the bone underneath,” he adds.
“Our results are potentially really good news for patients with OA,” says Cao. “We are already working to develop a clinical trial to test the efficacy of locally applied TGF-beta 1 antibodies in human patients at early stages of OA.” If successful, their nonsurgical treatment could make osteoarthritis—and the pain and debilitation it causes—halt in its tracks, he says.