Protein Loss Causes Cartilage Degeneration in Osteoarthritis

HMGB2 Is Related to Aging and Cartilage Degeneration

X-rays showing severe osteoarthritis in the knee.
X-rays showing severe osteoarthritis in the knee.. SMC Images/Getty Images

The Cause of Cartilage Degeneration

Researchers have long tried to determine what causes cartilage degeneration associated with osteoarthritis. A breakthrough by scientists points to the loss of a specific protein from the surface layer of cartilage in joints. That protein, referred to as HMGB2, appears to play a key role in cartilage degeneration.

Here's What Happens in Cartilage Degeneration

Articular cartilage is the hard but slippery tissue lining the bones within a joint, allowing smooth motion.

Cartilage is produced and maintained by chondrocyte cells, and includes fibrous collagen and mesh-like proteoglycans.

Osteoarthritis starts when there is a disruption at the surface layer of cartilage -- also referred to as the superficial zone. The surface layer is the most important of the four layers of cartilage in a joint, in terms of proper joint motion. Normal joints have a smooth surface layer of cartilage that allows joints to glide over one another. Cartilage also stabilizes joints and absorbs force. When the surface layer begins to deteriorate, though, osteoarthritis starts to develop and an irreversible process is initiated that ultimately destroys underlying layers of cartilage until the end-stage occurs: bone is rubbing on bone in the joint.

Researchers have known that the beginning phase of osteoarthritis was associated with deterioration of cartilage in the surface layer. What researchers now know is that even before the destruction in the surface layer occurs, there is loss of the DNA-binding protein, HMGB2.

More About HMGB2 and its Role in Cartilage Health

On the surface layer of cartilage in joints, HMGB2 supports chondrocyte survival. Chondrocytes are the only cells found in cartilage -- they actually produce cartilage. Simply put, the loss of HMGB2 is associated with aging and with chondrocytes being either reduced or eliminated in the surface layer of cartilage.

If HMGB2 is the key healthy chondrocytes, it points the way to developing new treatments to maintain cartilage and prevent its degeneration.

What This Breakthrough Means for the Future

What's the significance of the finding? It came from a collaboration among researchers from Scripps Research Institute in La Jolla, California; San Raffaele University in Milan, Italy; and Kogoshima University in Japan.

The potential future paths of research can go in two directions. They could look for molecules that would stop the loss of HMGB2 and develop them into treatment drugs. They could look for ways to stimulate production of HMGB2, especially for people who have already had cartilage loss, repairing cartilage. Osteoarthritis conceivably could someday be either prevented or reversed. The discovery of the role of HMGB2 in osteoarthritis may also impact how stem cells are used in tissue regeneration in the future.

It may turn out that HMGB2 is only a small part of the picture of cartilage degeneration.

Research often produces an exciting clue that ultimately turns out to be a dead end. It may not be possible to find a drug that affects HMGB2 in the way needed to repair and build cartilage. But each new clue and new link in the chain can lead to progress in prevention and treatment of osteoarthritis.

Source:

Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis. Tanaguchi N et al. PNAS. January 12, 2009 (online).
http://www.pnas.org/content/early/2009/01/12/0806062106.abstract

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