Scientists Seek Relief for Aching Joints

The debilitating effects of osteoarthritis impact an estimated 27 million Americans, forcing them to adjust their everyday lives, from work to social activities, to limit the pain in their joints. The cause of arthritis is unknown, but NC State researchers have turned to the somewhat odd combination of pig knees, synthetic fluid, and mathematical formulas to study the chronic condition from different perspectives. They hope to understand it better so treatments can eventually be developed.

People are more likely to develop osteoarthritis if they’ve previously had a joint injury, says Dr. Peter Mente, an associate professor of biomedical engineering. So he routinely obtains porcine joints from a Burlington sausage plant and brings them back to his lab, where a device he assembled hammers and twists them to simulate an impact like slamming your knee into your car dashboard during a collision. Banging on the erstwhile ham hocks lets his research team study how the cartilage in the joints responds to injury.

Mente’s experiments show that many chondrocytes, the cells in cartilage, die on impact. Others that are seriously damaged basically shut themselves down to die later on, with the number of cell deaths spiking within two weeks. The loss of chondrocytes causes the cartilage tissue to break down, he says, increasing the wear and tear on the joint. Although the surviving chondrocytes attempt to rebuild the tissue, the new molecules being made are often not the same as those in a normal, healthy joint. “These cells aren’t programmed to do a lot of repair,” Mente says. “So what comes back after an injury usually isn’t as good as what was there before.”

“The mechanical and physical surroundings have an important function in regulating the health of the cells.”

Mente is now working with Dr. Melissa Ashwell in the Department of Animal Science to examine changes in gene expression and metabolic pathways in chondrocytes after an injury. He also is working with colleagues at the College of Veterinary Medicine Small Animal Hospital to compare his post-injury findings with instances of naturally occurring osteoarthritis. “You usually don’t know cartilage is eroding until you’ve got bone-on-bone contact,” Mente says, noting the tissue has no blood supply or nerves. “We’re trying to trace it back to see if there are markers that can help diagnose it earlier.”

One marker Dr. Mansoor Haider has noted is changes in the mechanical and physical properties of chondrocytes.
The associate professor of mathematics has developed models to study how the cells respond to different forces. He is working with a Duke University Medical Center orthopedic lab that harvests chondrocytes and their protective “capsule” of collagen—together they’re known as chondrons—from surgical waste following joint replacement operations. Computing the differential equations in his models allows Haider to subject the chondrons to a variety of stresses, strains, fluid shears, and changes in ion concentration. “The mechanical and physical surroundings have an important function in regulating the health of the cells,” he says. “Any disruption of the environment can throw them off balance.” He uses these models to confirm clinical findings of the Duke researchers and to provide them with leads to study.

“If we can understand the role and importance of the different systems affected by osteoarthritis, the design of better, targeted treatments might be possible.”

In one study, for example, Haider developed a formula to estimate stiffness of the chondron’s outer capsule by measuring how much a chondron isolated in the lab deformed when suction was applied. He determined that the stiffness decreases by 40 percent in arthritic tissue. In a follow-up study, computational models simulated stresses and strains in the cellular environment of cartilage subjected to dynamic compression. The simulations demonstrated that the capsule acts as a “mechanical transducer” as well as a protective layer for the cell, and that osteoarthritis alters both functions. “We believe the cells use strain to detect and respond to alterations in their surroundings,” he says. “Strain can be a good thing if it’s not too great.”

Cartilage isn’t the only part of a joint affected by the onset of osteoarthritis. Dr. Wendy Krause, a polymer scientist in the College of Textiles, is studying changes to the synovial fluid that lubricates the cartilage. The fluid, which also supplies nutrients to and removes waste products from the chondrocytes, has always fascinated Krause because of its unusual mechanical properties. For example, its viscosity increases over time under a steady shear force.

A healthy joint lubricated by synovial fluid has roughly the same amount of friction as a sharp skate on a sheet of ice, says Krause, whose research team blended a synthetic synovial fluid to model changes to the fluid found in arthritic joints. They combined saline, a biopolymer known as hyaluronic acid, and plasma proteins albumin and gamma globulin, then varied the concentrations of the proteins as they tested the model fluid with a nanoindenter. The device drags a tiny diamond tip through a drop of the fluid to measure friction and viscosity. Krause’s tests have shown the concentration of proteins to be critical to maintaining a low level of friction. “If we can understand the role and importance of the different systems affected by osteoarthritis,” she says, “the design of better, targeted treatments might be possible.”

 

Dr. Peter Mente observes as doctoral student Richard Shoge prepares a porcine kneecap for a test that simulates an impact injury to the joint.

Dr. Mansoor Haider uses mathematical models to study how cartilage cells respond to different stresses and strains.

Dr. Wendy Krause puts samples of synovial fluid her research team created into a nanoindenter to study the changes in friction produced by variations in proteins in the fluid.

The causes of osteoarthritis are unclear, but NC State researchers are using various means to study the onset of the condition and the changes it produces in cartilage and the surrounding synovial fluid in joints.