Bioengineers delve into what joints need to function.

Compared to joints grown alone in a bioreactor (left panel) those additionally exposed to joint-flexing machines (right panel) increase their cartilage cells' production of proteoglycan 4 (purple), a key component in synovial fluid.

To get up and go, we need our joints. But what happens when they give out? Joint replacement surgery is an option, but one day scientists hope to regenerate failing joint tissue. Getting a step closer to this goal is HHMI professor Robert L. Sah from the University of California, San Diego, who with a team including undergraduate students designed a bioreactor capable of growing cartilage tissue within whole joints.

Due to aging and normal wear and tear, the smooth surface of cartilage at the ends of bones in joints erodes and synovial fluid is unable to effectively lubricate the joints, which can lead to the painful condition known as osteoarthritis. The damaged joints can be replaced with artificial ones, but doctors would rather be able to resurface existing joints with a patient's cartilage.

Sah's team found that applying shear load to a joint, as is done with the machines that gently flex patients' knees to help them recover from joint surgery, causes cartilage cells at the edge of the joints to produce a molecule called proteoglycan 4. Like oil in an engine, proteoglycan 4 appears to be a necessary component in synovial fluid for normal joint lubrication and function.

The results are reported in a November 21, 2006, online article of Osteoarthritis and Cartilage.

Sah hopes one day to be able to culture pieces of joint tissue from arthritic patients back to a healthy form, and then reimplant them. For this to occur, he and others need to figure out what factors are needed to grow cartilage and create the synovial fluid that flows between the joints.

"Like an enzymatic cascade, there may be a mechanical cascade of events that needs to occur for cartilage to grow and mature," says Sah. "If we can dissect the mechanobiologic process into distinct components, then we could potentially reengineer the process to regenerate cartilage and joints."

Photo: Image adapted from Osteoarthritis and Cartilage 2006, Nugent-Derfus, G.E. et al., epub doi:10.1016/ j.joca.2006.10.1015.