Sci. Aging Knowl. Environ., 23 February 2005
Protein keeps joints from seizing up
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2005/8/nf15
A downhill racer needs a good wax to keep her skis gliding, and her knees also need lubrication. A new study of mice shows how one protein keeps joints such as the knee flexible. Without it, certain cells grow beyond their usual boundaries, causing cartilage to deteriorate and joints to stiffen. Mutations in the gene for this protein underlie a rare human disease, and more subtle changes might contribute to arthritis.
Cartilage coats the ends of bones and helps them move smoothly in joints. But when cartilage deteriorates, joints can become immobile. Rheumatoid arthritis results when inflammation attacks joints, whereas osteoarthritis develops from wear and tear on the skeleton. A capsule called the synovium surrounds joints and contains a fluid that lubricates them. A layer of synovial cells produces the fluid and helps clean it. Previously, geneticist Matt Warman of Case Western Reserve University in Cleveland, Ohio, and colleagues found that mutations in a protein produced by synovial cells, known as lubricin, cause a rare disease in which fingers stiffen and joints enlarge. To further investigate lubricin's function, the researchers removed the gene from mice.
By 4 months of age, the animals' ankles had swollen, they couldn't flex their hind legs, and they walked awkwardly. When the scientists examined the animals' elbows and knees, they found that the synovial cell layer had grown abnormally thick and crept onto the cartilage. As animals aged, the synovial layer thickened even more, and the cartilage warped and accumulated a protein coat.
To pin down the fault in synovial cells, the researchers cultured cells from normal and altered animals. Control cells divided only twice, whereas cells without lubricin split multiple times. When the team coated culture plates with lubricin, altered cells couldn't stick to the surface or reproduce. But they clung to plates without the protein. Moreover, adding lubricin after cells had attached didn't block their growth. Those findings suggest that lubricin helps curtail cells' proliferation by preventing them from adhering to surfaces, a function that meshes with previous predictions based on the protein's amino acid sequence.
Researchers knew that lubricin kept joints slippery, says bone biologist Ernst Hunziker of the University of Bern in Switzerland, "but the new thing is the protection from adhesion." Lubricin snafus might contribute to rheumatoid arthritis, in which synovial tissue also thickens. Arthritis researcher Stefan Lohmander of Lund University in Sweden says that changes in lubricin could exacerbate the more common osteoarthritis, as well. For instance, older people might produce less lubricin. Warman notes that lubricin quantities plummet when injured joints get inflamed. Lubricin's absence might increase friction enough to roughen sections of joint surfaces like scratches on a nonstick pan. Those nicks might continue to wear away, even after inflammation cools and lubricin returns, gradually sloughing off cartilage over a lifetime, he says. If so, injections of lubricin or drugs that prevent its breakdown might help smooth the ride for older joints.
February 23, 2005
Science of Aging Knowledge Environment. ISSN 1539-6150