Their findings came to light while the researchers were studying the different ways in which cells in human blood vessels and joints respond to pressure gradients generated from liquid moving along their surface. In cells that line blood vessels, the reaction to that shear stress is beneficial: the boosting of phase 2 enzymes that may protect the cells from cancer-causing chemicals and other toxic agents.
Yet in joints, the response to high shear stress is potentially harmful: an increase in the levels of COX-2 enzyme, which triggers inflammation and pain, and suppresses the activity of phase 2 enzymes, ultimately causing the death of chondrocytic cells. When chondrocytes stop functioning properly, the result can be arthritis.
The researchers obtained compounds that boost the activity of helpful phase 2 enzymes. They added these inducers to a dish containing chondrocyte cells. After 24 hours, the cells were subjected to a stress test designed to mimic aspects of strenuous exercise on a joint as well as the hydrodynamic environment in a bioreactor designed to generate artificial cartilage.
"The beneficial phase 2 enzymes somehow seemed to prevent the activation of the inflammatory COX-2 enzyme," said Zachary R. Healy, doctoral student in Konstantopoulos' lab. "The phase 2 enzymes inhibited the inflammation and the apoptosis - the cellular suicide we'd observed. That means these compounds could be useful as a preventive measure, perhaps before strenuous exercise," Healy said.
By showing a way to ward off inflammation and by providing insights into the effects of shear stress, the new chondrocyte research may also aid tissue engineers who are trying to grow artificial cartilage or seeking to revitalise human cartilage in the lab. This is important because human bodies cannot make new cartilage to replace tissue that's lost to injury or disease.
MEDICA.de; Source: Johns Hopkins University