Researchers Find Clue to Degradation of Cartilage in Osteoarthritis

Researchers at Case Western Reserve University have found kinks in aggrecan, a protein at the submolecular root of arthritis, which may bring scientists closer toward new therapies to prevent or treat the disease.

"Aggrecan acts to organize and densely pack sugar molecules that give cartilage its resilience," said Steven Eppell, assistant professor of biomedical engineering. "Our research shows that aggrecan is sharply bent in specific places and more flexible in other regions, and that the kinked areas may be more susceptible to the enzymes that degrade cartilage in osteoarthritis."

Researchers examined the protein structure using an atomic force microscope. Using sophisticated image processing, they mapped images of aggrecan onto the human genome and found that the kinks in their images lined up with places where aggrecan gets corrupted in osteoarthritis, showing a link between aggrecan's structure and its function.

"Clarifying the functions of more than 30,000 proteins that make up the proteome is a major challenge in the wake of the human genome project," said Eppell. "Studying human proteins and discovering how they interact inside their microscopic three dimensional world is a path leading scientists closer to linking a disease with its genetic characteristics. Trailblazing these paths requires us to investigate these proteins, one at a time, to learn how they interact inside their own three-dimensional world and in the body."

"We are working vigorously to link the biological and mechanical properties of cartilage with its molecular structure," continued Eppell. "Ultimately, we are in search of clues that lead to intelligent drug design and other interventions to prevent or alleviate arthritis."

Other sources: Case Western Reserve University