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Studies Hold Promise of Understanding Arthritis

In work that could help diagnose arthritis before it is well underway and potentially untreatable, an MIT electrical engineer and colleagues are developing a technique to study cartilage, the tissue that is destroyed by the disease.

Cartilage functions primarily as a kind of cushion between abutting bones. Currently, however, it is difficult to examine the tissue in the body. "So typically by the time doctors diagnose arthritis, the disease is very far along and, on average, treatment is for pain relief," said Martha L. Gray, principal researcher in the study and J.W. Kieckhefer Assistant Professor of Electrical Engineering.

Basic research on arthritis also suffers. "It's very difficult to understand a disease when there is no way to watch its natural progression in the body," Professor Gray said. As a result, scientists still know relatively little about the development of cartilage disease.

The technique Professor Gray, Leann M. Lesperance and Deborah Burstein are developing uses nuclear magnetic resonance (NMR) to measure slight changes in the composition of cartilage. All three researchers are associated with the Harvard-MIT Division of Health Sciences and Technology. Ms. Lesperance is a graduate student in HST; Dr. Burstein, who received the SM in 1982 and PhD in 1986 from MIT, is an NMR specialist at Beth Israel Hospital.

The researchers recently showed that the NMR technique can measure the amount of proteoglycan, one of two principal constituents of cartilage, in samples of nonliving tissue. The work, which is directly applicable to living tissue, was published in this month's Journal of Orthopaedic Research. It is important because changes in proteoglycan and collagen, the other major constituent of cartilage, can indicate disease.

For example in osteoarthritis, for reasons that are not completely understood, proteoglycan and collagen in the cartilage cushion are slowly degraded, until eventually the cushion is destroyed and the joint must be replaced. The NMR technique could help catch the disease in its early stages. From there, doctors could use the technique to monitor treatments that might save the joint.

The NMR study is one of several led by Professor Gray to better understand cartilage and answer critical questions about it. For example, scientists believe that cartilage can adapt to different levels of physical activity over time. Much like muscle, it grows "stronger" with exercise or "weaker" with inactivity. But how do cartilage cells know when to produce more or less of the tissue associated with these changes? As Professor Gray explained, "Somehow the cartilage cells can accumulate information on whether the cartilage tissue is receiving more or less mechanical load."

Actually, the cartilage cells themselves make up less than 10 percent of the tissue. Unlike organs such as the liver, which is composed mostly of cells, cartilage is composed mostly of a spongy matrix. The composition and architecture of this matrix, made principally of proteoglycan and collagen, is controlled by the cartilage cells. As a result, a major focus of Professor Gray's research is to "determine the relationship between mechanical load and what the cells do to create or degrade the matrix over the long term."

To study this problem Professor Gray has divided her work into two general groups: one to develop nondestructive techniques to study the proteoglycan/collagen matrix (the focus of the NMR work) and one to study the cartilage cells.

In one part of the cell work Professor Gray is collaborating with Lee Gehrke, an associate professor in the Harvard-MIT Division of Health Sciences and Technology, to explore whether on the cellular level mechanical loads, or exercise, can alleviate the effects of a compound associated with arthritis.

Scientists already know that mechanical loads somehow trigger cartilage cells to change the rate at which they make the proteoglycan/collagen matrix. They also know that the compound interleukin-1, or IL-1, leads to the degradation of the proteoglycan/collagen matrix (IL-1 is found in the joint fluid of patients with rheumatoid and sometimes osteoarthritis).

But how do the two interact? Said Professor Gray: "Can we prevent cells from responding to IL-1 if we add a mechanical force?" On the other hand, could mechanical loads make things worse? "We want to know whether a patient should run, walk or stay in bed," Professor Gray said.

To address these questions the scientists are working with small discs of living cow cartilage. They are running a number of tests on the tissue, including adding IL-1 and watching how the cartilage responds, and adding both IL-1 and some mechanical load and watching that.

The study is still too young to draw any conclusions. Taken together, however, the cell studies and the NMR work present a formidable assault on the mysteries and diseases of cartilage.

A version of this article appeared in the January 29, 1992 issue of MIT Tech Talk (Volume 36, Number 18).

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