Lee DM, Kiener HP, Agarwal SK, et al. Cadherin-11 in synovial lining formation and pathology in arthritis. Science. E-pub ahead of print January 25, 2007.
A new development by researchers supported in part by the Arthritis Foundation have uncovered a new pathway that regulates joint destruction associated with inflammatory arthritis. Current and previously Foundation-funded researchers David M. Lee, MD, PhD, and Michael Brenner, MD, of Brigham and Women’s Hospital, Harvard Medical School in Boston and an international team of scientists found that blocking the action of a protein called cadherin-11 prevents the joint destruction that characterizes inflammatory arthritis in laboratory mice. They are hopeful that their success in mice will lead to a new treatment option for people with rheumatoid arthritis and other inflammatory joint diseases.
What problem was studied?
Synovial tissue is found between surfaces of joints. When a person has inflammatory arthritis, such as rheumatoid arthritis, the synovial tissue overgrows to form a pannus, which attaches to and invades bone and cartilage surfaces, destroying them. Cadherins are molecules that provide adhesion between cells, contributing to the maintenance and integrity of tissues. Dr. Lee and colleagues set up a series of experiments to determine the role of cadherin-11 in the organization and integrity of synovial tissue and pannus.
What was done in the study?
The research team studied synoviocytes, cells that form synovial tissue. One cell line that they studied was unable to produce cadherin-11 and the other was capable of producing the adhesion molecule. They then watched what happened when the cells began to form synovial tissue. After studying the cell lines, the scientists studied mice specially bred to develop autoimmune arthritis, some of which could produce cadherin-11 and some of which could not. Next, they examined cadherin-11 as a therapeutic target against autoimmune arthritis in these mice.
What were the study results?
Drs. Lee and Brenner’s team discovered that when there is no cadherin-11 present in inflamed joint tissue, the structural changes associated with pannus formation on cartilage do not occur. Furthermore, they found that by administering a chemical that interfered with the function of cadherin-11, inflammatory arthritis could be prevented in mice who had not yet developed the disease and could be alleviated in mice with established arthritis.
In cadherin-11 deficient mice with genetic arthritis, synovial tissue invasion into cartilage was “markedly diminished.” Looking at the synovium under the microscope, the researchers were able to determine that there was an 80% reduction in cartilage erosion in the cadherin-11 deficient mice compared with the mice that could synthesize cadherin-11.
What Does This Mean for People with Inflammatory Arthritis?
These results in mice are very encouraging for people with rheumatoid arthritis. Dr. Lee and Dr. Brenner’s team have identified another therapeutic target, a discovery that may lead to a new drug to treat arthritis.