Chondroitin Sulfate and Hyaluronic Acid Size as Indicators of Joint Disease

The lubricating fluid of the joint, called synovial fluid, contains long chains of sugar molecules called glycosaminoglycans (GAGs). The major GAG in the fluid is hyaluronan. Hyaluronan contributes to the synovial fluid’s lubricating properties and also controls fluid flow into and out of the joint space. It is sometimes injected into knee joints with osteoarthritis (OA) to ease pain and stiffness. Chondroitin sulfate, another GAG, is a structural component of aggrecan in cartilage and provides much of its resistance to compression. Chondroitin sulfate has become a popular nutritional supplement that people take with the hope of easing joint pain and stiffness.

What Problem Was Studied?

These two GAGs have been widely studied as biomarkers of metabolic changes in joints, including as markers of OA. However, studying GAGs as markers of early OA in humans has been difficult because synovial fluid samples of people with very early OA are rarely available since people don’t tend to seek treatment until their symptoms become severe.

Researchers from the University of Florida in Gainesville and University of South Florida in Tampa, including Arthritis Foundation-funded scientist John D. Sandy, PhD, currently at Rush University, Chicago, have been using the horse as a model of OA for assessing early changes in the GAGs of synovial fluid.

What Was Done in the Study?

Three groups of horses were studied: 1) Healthy horses after eight weeks of pasture rest; 2) the same horses after nine months of strenuous treadmill training; and 3) horses brought to the veterinarian for lameness due to osteochondral fracture (quite common in thoroughbred race horses). The size (chain length) of the chondroitin sulfate and hyaluronan molecules were compared among the groups, and relationships between the molecules’ size and the health of the joints were sought.

What Were the Study Results?

The research team found that the chondroitin sulfate chain length was longest in the injury group, of intermediate size in the exercise group and shortest in the rested group. Because chondroitin sulfate is made within and released from the cartilage, these results suggest that injury, and to some extent exercise, causes the production of abnormally long chondroitin sulfate on aggrecan, which is not retained by the tissue. They also demonstrated that osteochondral injury (injury to the cartilage and underlying bone caused by the pounding of racing) triggered a significant decrease in hyaluronan chain length and total concentration in the synovial fluid. Since the hyaluronic acid is made mostly by the jointlining cells (synoviocytes), these results suggest that injured joints are unable to make the normal long hyaluronan that is critical to joint function.

What Does This Mean to People with Arthritis?

The team determined that measuring the length of chondroitin sulfate and hyaluronan in synovial fluid could be used to determine the extent of joint disease following injury due to trauma or overuse. The authors concluded, “Based on these findings, chain length analysis of synovial fluid chondroitin sulfate and hyaluronan may provide a useful tool for evaluation of joint health.”

What this could mean in the future is that if a person has joint pain, a small sample of synovial fluid could be analyzed. If the GAG chain lengths indicate joint injury or trauma, measures could be taken to prevent further deterioration of the joint or even the onset of osteoarthritis. According to Sandy, “The most important message is that joints are extremely sensitive to injury and overuse and sensible lifestyles that avoid joint trauma could eliminate a high percentage of the cases of osteoarthritis, which will doubtless occur in the coming years.”

Brown MP,TrumbleTN, Plaas AH, Sandy JD, Romano M, Hernandez J, Merritt KA. Exercise and injury increase chondroitin sulfate chain length and decrease hyaluronan chain length in synovial fluid. Osteoarthritis Cartilage 2007.

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