Lubricin research points to future therapies for osteoarthritis

Apr 11 2006

New evidence to explain how the body's natural joint lubricant prevents the wear and tear that can lead to osteoarthritis has been uncovered by researchers at Duke University's Pratt School of Engineering.The findings may lead to new methods for treating arthritis, the researchers said.

The team found in realistic models of joints that, rather than simply reducing friction, a component of joint fluid called lubricin forms a very thin barrier that repels joint surfaces to prevent their contact. The researchers further found that lubricin in combination with a second constituent of joint fluid known as hyaluronic acid (HA) produces an even greater protective effect than either of the components alone.

Collaborators on the study include Stefan Zauscher and Nehal Abu-lail, of Duke's Pratt School; Farshid Guilak, of the Duke University Medical Center; and Gregory Jay, of Rhode Island Hospital in Providence.

"In the healthy joint, the intact superficial surface layer of cartilage provides an extremely efficient bearing surface with an apparently very low coefficient of friction," said Zauscher, an assistant professor of mechanical engineering and materials science at Duke's Pratt School.

"Any damage to this superficial zone or absence of lubricating factors may be the cause of a cascade of mechanical failures in joints that ultimately leads to the onset of osteoarthritis," he said. Zauscher is also a member of the Center for Biologically Inspired Materials and Material Systems at Duke.

Through careful measurement of forces acting on models that mimic interacting joint surfaces at the molecular level, the researchers have begun to determine the mechanisms by which lubricants provide protection in limb joints characterized by bony surfaces covered in a layer of cartilage, Zauscher said. Lubricin appears to reduce adhesion between joint surfaces and may also cover the joint surface with a protective layer that physically prevents cartilage from running up against each other.

Three constituents of joint fluid -- lubricin, HA and lipids -- are thought to play a role in mediating friction. However, a recent study by other researchers found that degradation of joint lipids had little effect on their lubrication, Zauscher noted.

Due in part to its larger molecular size, research efforts have focused more attention on HA. Indeed, physicians currently treat osteoarthritis with HA injections, Zauscher said. While such treatment can reduce pain and inflammation, the therapy seems to do little to protect joints from further damage, he added.

While scientists had speculated that lubricin contributes to the unique frictional properties of the joint, the mechanism by which it prevents wear has been controversial, Zauscher said.

"Considering the extensive impact and consequences of osteoarthritis, little is still known of its etiology and details of the boundary lubrication mechanism have remained unclear," Zauscher said. "The uncertainty stems primarily from the complex chemical and structural properties of the bearing surface, and the lack of suitably developed measurement approaches."

A new method developed by the researchers allowed for the first direct measurements of the forces on model joints using atomic force microscopy (AFM). AFM is a technique for analyzing forces on the surface of materials all the way down to the molecular level. The researchers tested the lubricating effects of model fluids containing varying concentrations of lubricin on the forces between a tiny bead and a glass slide, both of which had chemically modified surfaces that mimicked those found in joints.

The researchers found that, in the presence of lubricin, molecular interactions between the ball and slide were always repulsive. The strength of the repulsive force rose as the concentration of lubricin increased until it reached a level at which the lubricant formed a continuous layer. While HA alone failed to have such an effect, a mixture of lubricin and HA produced a greater repulsive force than either substance alone, they found.

"It appears that an important role of lubricin is not to reduce friction, but rather to protect sliding surfaces from wear by forming a barrier between them," Zauscher said.

The findings have important clinical implications for the development of future therapies for osteoarthritis, as well as for patients with a rare genetic disease, in which their joints cannot produce functional lubricin.

The team will next examine the lubricant's role in keeping joints limber using methods they have developed to directly measure joint friction in normal mice and in genetically modified mice that lack lubricin.

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