Collagen Defect May Trigger Osteoarthritis

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Arthritis develops five times faster in joints that lack a specific type of collagen.

That’s what researchers reported Feb. 20 at the Orthopedic Research Society annual scientific meeting in Washington, D.C.

They believe the discovery—based so far only on studies in animals—provides a vital new clue to understanding why more than 20 million Americans develop osteoarthritis, the so-called “wear-and-tear” form of the disease.

Osteoarthritis, the most common form of arthritis, results from the degeneration of joint cartilage and is a leading cause of disability in the United States, according to the American College of Rheumatology. Osteoarthritis can affect most joints, including the neck, lower back, hips, knees and fingers.

In the study, animals who lacked type VI collagen got arthritis five times faster than those who did not lack the collagen. Collagen is a protein found throughout the body in muscle, connective tissue, cartilage and bone, and numerous types of collagen have been identified.

As a result of the study, “we have a much better understanding of the role of type VI collagen’’ in cartilage, said lead author Leonidas Alexopoulos, a postdoctoral researcher at the Massachusetts Institute of Technology, who completed the research while a graduate student at Duke University.

Alexopoulos and his colleagues evaluated a narrow region of tissue that surrounds the cartilage cells on the joint’s surface, known as the pericellular matrix (PCM). Collagen type VI (as well as other types), along with cartilage cells and the PCM, form a structure called a chondron, which is thought to provide a “buffer zone” between these cartilage cells and the remainder of the cartilage.

The team evaluated three groups of mice: one with normal type VI collagen genes producing normal amounts of the collagen; another group in which researchers had genetically engineered both parents to have the type VI collagen gene knocked out, and a third group in which just one parent had the type VI collagen gene knocked out.

When the mice were 6 months old, the researchers removed their chondrons—the structures believed to provide a buffer between the cells and the remainder of the cartilage—to see how they held up.

According to the researchers, 73 percent of the mice whose parents both lacked the type VI collagen gene showed evidence of mild to moderate arthritis, compared to 40 percent of those with one parent lacking the gene, and just 13 percent of the mice with normal type VI collagen production.

The study suggests that type VI collagen serves as a kind of protective scaffold that provides structure and stiffness to the PCM, the researchers said.

Another expert in the relationship between collagen and arthritis, Dr. Roland Moskowitz, called the new research “interesting and exciting.”

Moskowitz, a professor of medicine at Case Western Reserve University, in Cleveland, and immediate past president of the Osteoarthritis Research Society International, helped discover a gene mutation involving type II collagen that leads to a form of familial osteoarthritis striking early in adulthood.

Researchers know there are numerous kinds of collagens, but their exact roles and effects on arthritis are not clearly known, Moskowitz and other experts said.

The new discovery that low levels of type VI collagen may help trigger arthritis “may prove to be very important,” Moskowitz said. “It may have widespread applications.” Down the line, he said, researchers might find an agent that could stimulate type VI collagen in those who produce too little.

“The findings are really interesting and dramatic,” said another expert, Dr. Charlene Williams, associate director of research in the division of rheumatology at Thomas Jefferson University, in Philadelphia.

However, “the problem is, we really don’t completely understand what type VI collagen does in cartilage,” Williams said. Nevertheless, the researchers “do present an excellent model system for the study of osteoarthritis, but there is still a lot of work to be done in order to understand the complete role of type VI collagen,” she said.

More information

To learn more about arthritis, visit the American College of Rheumatology ( http://www.rheumatology.org).

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