Molecular Repair Of Ruptured Discs

Their findings, reported in the January 15th Journal of Clinical Investigation, could lead to the development of non-surgical treatments for herniated discs. Low back pain is a common problem, affecting between 60 and 80 percent of Americans during their lifetime, and most of this pain is presumed to be disc-related, said Dr. Dan M. Spengler, professor and chair of Orthopaedics and Rehabilitation.

"There are a lot of disc surgeries-up to 300,000-each year in the United States," Spengler said.

The intervertebral discs that separate the spine's vertebrae act as shock absorbers, allowing the spine to bend and flex. Physical trauma to the spine-for example from something as simple as bending forward while lifting a heavy object-can cause the outer cartilage ring of a disc to rupture. The semifluid disc filling then spills out and presses on nerves, resulting in low back pain and sciatica, shooting pain in the legs.

"We know that about half of patients with disc herniation will improve within six weeks, and that the herniation may be completely resolved over time," Spengler said. "The interesting question is: why doesn't everyone have this spontaneous resorption?

"Understanding what causes the resorption process is a first step to the future development of medication that would predictably remove the herniation." Dr. Hirotaka Haro, a visiting orthopaedic surgeon from Japan, initiated a collaboration with Lynn M. Matrisian, Ph.D., professor and interim chair of Cell Biology, to examine the molecules at work in herniated disc resorption. Haro had previously demonstrated that proteins called matrix metalloproteinases (MMPs) are present in herniated disc samples. Since MMPs chew through other proteins in Pacman-like fashion, it makes sense that they might participate in dissolving the protruding disc.

Other investigators had observed that different cells are present in herniated disc samples compared to normal discs. Macrophages, immune system cells that ingest microorganisms and foreign materials, are particularly prevalent. "In fact, the clinical literature suggests that contact of the herniated disc with the blood supply is important to the resorption process," Matrisian said. "So the more that the herniation extends and protrudes into the spinal cord-in essence the worse it is-the more likely it is that it will resorb by itself." Haro wanted to put these two observations together and probe the role of MMPs and disc/macrophage interactions in disc resorption, and Matrisian had the perfect tools: knockout mice that lacked the MMPs matrilysin and stromelysin. These two MMPs just happened to be the specific ones that Haro had found in herniated disc samples.

To study resorption, Haro developed a culture system that mimics what is happening in the herniated disc. He isolated discs and macrophages from mice and put them together in the same culture dish.

"Hiro was able to dissect the tiny discs from the tails of these mice and add macrophages to them to re-create the conditions in the herniated disc," Matrisian said, "a