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Bone joint: use it or lube it

The surface (top) of joint cartilage has the highest concentration of chondrocyte cells, which are crucial to maintenance of a wear-resistant surface.
The surface (top) of joint cartilage has the highest concentration of chondrocyte cells, which are crucial to maintenance of a wear-resistant surface.

Taking a cue from machines that gently flex patients' knees to help them recover faster from joint surgery, UCSD researchers have shown that sliding forces applied to cartilage surfaces prompt cells in that tissue to produce molecules that lubricate and protect joints.

The results reported in Osteoarthritis and Cartilage are important in the ongoing efforts of the group led by Robert Sah, a Howard Hughes Medical Institute (HHMI) professor of bioengineering in the Jacobs School.

"We have shown that shear forces on cartilage prompt chondrocyte cells in it to produce proteoglycan 4," says Sah. "This is an important step toward our goal of eventually growing joint tissue for transplantation."

Proteoglycan, which is made of protein and polysaccharide components, comprises connective tissue throughout the body. Chondrocyte cells of cartilage make several forms of proteoglycans, including several that build up in cartilage and contribute to its stiffness. However, proteoglycan 4 is primarily secreted into the joint fluid where it coats and lubricates cartilage surfaces.

The team measured up to a three-fold increase in chondrocytes secreting proteoglycan 4 in continuously flexed joints compared to immobile controls. The flexing motion caused cartilage on the surfaces of opposing bones to slide against each other, creating so-called shear forces. In one continuously sliding cartilage surface, 40 percent of the chondrocytes were secreting proteoglycan 4, whereas in immobilized joints only 13 percent of the chondrocytes were secreting it.

Cartilage subjected to continuous passive motion (right) has more chondrocyte cells producing a lubricant called proteoglycan 4 than when cartilage is not moved (left). Cartilage subjected to continuous passive motion (right) has more chondrocyte cells producing a lubricant called proteoglycan 4 than when cartilage is not moved (left).
Cartilage subjected to continuous passive motion (right) has more chondrocyte cells producing a lubricant called proteoglycan 4 than when cartilage is not moved (left).

Scientists know that defects in a gene for proteoglycan 4 result in a type of childhood joint failure that resembles osteoarthritis in the elderly. Sah's goal is to stimulate healthy chondrocytes in cartilage tissue grown in the laboratory to form robust tissue that makes proteoglycan 4 and has a smooth, well-lubricated surface.

The Osteoarthritis and Cartilage paper was co-authored by Sah, Gayle E. Nugent-Derfus, now an engineer at Genentech, Inc., Dr.William D. Bugbee, associate adjunct professor of orthopaedics at UCSD, and 13 researchers at UCSD, including six undergraduates.

Bioengineering professor Robert Sah supervises a laboratory where undergraduates learn from graduate students and post-doctoral fellows.
Bioengineering professor Robert Sah supervises a laboratory where undergraduates learn from graduate students and post-doctoral fellows.