A characteristic feature of osteoarthritis, progressive deterioration of cartilage, is due to the loss of the protein HMGB2; Scripps research scientists recently discovered.
The researchers showed how the loss of HMGB2, found in the surface layer of joint cartilage, leads to degeneration of cartilage in people suffering affected by osteoarthritis.
Advertisement"We have found the mechanism that begins to explain how and why aging leads to deterioration of articular cartilage. Our findings demonstrate a direct link between the loss of this protein and osteoarthritis," said Scripps Research Professor Martin Lotz, M.D., a world-renowned arthritis researcher who led the study with Noboru Taniguchi, M.D., Ph.D., a senior research associate in his lab.
Typically, osteoarthritis begins with a disruption of the surface layer of cartilage, called the superficial zone, which triggers an irreversible process that eventually leads to the loss of underlying layers of cartilage until bone begins to grind painfully against bone.
Osteoarthritis most commonly affects the spine, temporomandibular joints, shoulders, hands, hips and knees.
"We knew that the first phase of osteoarthritis is the destruction of cartilage in the superficial zone. Now we know that before this layer is destroyed, there is loss of the critical DNA binding protein HMGB2 and that this loss is directly related to aging," said Lotz.
It was found that the protein HMGB2 is uniquely expressed on the surface layer of cartilage in joints, where it supports the survival of chondrocytes, the cells that produce and maintain cartilage.
Aging is associated with the loss of HMGB2 and an accompanying reduction or total elimination of chondrocytes in the superficial zone.
In fact, the scientists provided further links between HMGB2 and osteoarthritis by genetically breeding HMGB2 deficient mice that had an earlier and more severe onset of osteoarthritis.
The findings provide a promising avenue to explore the development of new osteoarthritis treatment options.
"If small molecules can be found to prevent or stop the loss of HMGB2, or conversely, to stimulate the production of this protein, then it is possible that osteoarthritis may one day either be prevented or reversed," said Lotz.
The finding may provide scientists with a clue about how they might be able to engineer the surface layer cartilage.
"As our population ages, osteoarthritis will become an ever-greater health issue. Everyone eventually gets osteoarthritis; even those people who are not functionally impaired by the disease are found to have cartilage damage. And it all starts with the loss of cells in the superficial layer. We now have a starting point for potential prevention, diagnosis, and treatment," said Lotz.
The scientists describe their work in this week's Early Edition of the Proceedings of the National Academy of Sciences.
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