Lubricant's Role In Keeping Joints Limber Comes Into Sharper Focus

The researchers say the finding offers the strongest evidence yet that treatments designed to increase levels of lubricin in humans may help stall the deterioration of arthritic joints.

The team found that the arthritic joints of mice lacking the gene that controls the production of lubricin show greater friction than do joints in normal animals. When observed at the molecular level, the surface of the mutant animals' joint cartilage also appears rougher and less stiff -- a finding that the researchers said suggests a loss of the cartilage's mechanical integrity without lubricin.

"Lubricin has been considered important, but the experiments had not been done," said Stefan Zauscher, a professor of mechanical engineering and materials science at the Pratt School. "This is the first look at the effects on biomechanics of lubricin's presence or absence."

Team member Jeffrey Coles, a Ph.D. student working in Zauscher's laboratory, presented the findings on Monday, Feb. 12, at the annual meeting of the Orthopaedic Research Society, in San Diego. The work was supported by the National Institutes of Health.

While lubricin had been suspected to play a role in reducing joint friction, earlier studies had focused on another constituent of joint fluid called hyaluronic acid. Injections of this material are frequently used as a treatment for osteoarthritis, the most common form of arthritis. However, the treatment seems to work primarily as an anti-inflammatory agent, Zauscher noted, doing little to prevent further joint damage.

Last year, Zauscher's group reported evidence that lubricin acts as a repellant boundary layer between joint surfaces, reducing friction by preventing contacts altogether rather than simply "greasing the wheels". Those results stemmed from the first examination of the changing molecular forces between a model joint and glass slide as the amount of lubricin in the solution between them increased.

Now, the researchers have applied a similar technique to the molecular-level study of mouse joints, comparing normal mice to those lacking the gene for lubricin. They used an atomic force microscope (AFM) to examine the cartilage found on the surface of the ball at the top of the thigh bone that fits into the hip socket of the mice.

AFM microscopes have a sharp tip that scans the surfaces of structures at the level of individual atoms and measures the force of molecular-level interactions. In this case, the team chemically modified the tip to imitate the chemical properties of joint cartilage.

The researchers used the modified tips to probe the surface of normal and lubricin-deficient joints, gaining measurements of the amount of friction between the two surfaces. They also obtained measurements of the roughness and stiffness of the cartilage surface.

When compared with mice that have normal joint cartilage, mice lacking lubricin showed two to three times the amount of friction and their joint surfaces were more than twice as rough. The stiffness of the joint cartilage in mutant mice also was reduced by a factor of five, the researchers found. They noted that these findings are consistent with the significant tissue degeneration in early osteoarthritis.

"It's clear from our findings that lubricin is important for protecting the structural integrity of joints," Coles said.

The researchers next will examine the effects of replacing lubricin on the joint surfaces of mutant mice. They are seeking a better understanding of how lubricin carries out its role as a boundary lubricant, leading perhaps to an improved treatment option for osteoarthritis. Preliminary evidence suggests that lubricin injections may prevent, or at least slow, further deterioration of joint cartilage in the arthritic mice.

Collaborators on the study included Farshid Guilak of Duke University Medical Center and Duke's Pratt School of Engineering; J. Cha and Gregory Jay of Brown University; and Matthew Warman of Case Western Reserve School of Medicine.