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Jefferson scientists show how collagen gene mutation leads to osteoarthritis

Scientists at Jefferson Medical College have shown how a genetic alteration in a type of collagen can lead to osteoarthritis. The researchers, led by Andrzej Fertala, Ph.D., assistant professor of dermatology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, analyzed a mutation in the gene for a type of collagen, collagen II, found in five unrelated families with several members who developed osteoarthritis at a young age. They found that the altered version of collagen doesn't properly mesh with another type of collagen necessary to form the structure of cartilage, resulting in the development of osteoarthritis.

"We found that the very critical interaction between collagen II and another collagen, collagen IX, is altered as a result of this particular mutation," he says. "The study showed that mutant collagen II is not able to form normal assemblies with collagen IX. The results indicate that mutations in collagen II cause alterations not only on the molecules that carry the mutation but, also, dramatically affect the behavior of normal proteins that function as their natural biological partners.

"We think because this precise framework of cartilage is severely altered, it can significantly contribute to the progression of osteoarthritis." The work, he says, "significantly extends the existing knowledge of how mutations in collagen genes are translated to disease."

Dr. Fertala and his co-workers report their results in December in the journal Biochemistry.

Collagens are structural proteins that provide structural strength to connective tissue, such as skin, bone and cartilage. Collagen II, together with the protein collagen IX, form a "biological alloy." This "alloy" is molded into a fibril-like structure and is arranged in a precise network, providing cartilage with great mechanical strength.

Researchers have previously shown that alterations in the gene for collagen II could contribute to the development of th
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Contact: Steve Benowitz
steven.benowitz@mail.tju.edu
215-955-5291
Thomas Jefferson University
11-Dec-2001


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