The discovery was detailed in a paper published in the Sept. 27 edition of Proceedings of the National Academy of Sciences.
The findings came to light while the researchers were studying the wildly different ways in which cells in human blood vessels and joints respond to pressure gradients generated from liquid moving along their surface, a force called shear stress. In cells that line blood vessels, the reaction to 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. Healthy chondrocytes are responsible for the smooth functioning of joints. When chondrocytes stop functioning properly, the result can be arthritis.
The divergent responses to shear stress prompted a series of experiments in a Johns Hopkins lab supervised by Konstantinos Konstantopoulos, associate professor of chemical and biomolecular engineering and Agarwal-Masson Faculty Scholar. His team knew that strenuous exercise or heavy exertion of muscles can cause joints to increase the levels of harmful COX-2 enzyme. What would happen, the researchers wondered, if the vulnerable chondrocyte cells in human joints were first exposed to the beneficial phase 2 enzymes?
To find out, the researchers obtained compounds that boost the activity of helpful phase 2 enzymes. They added these phase 2 induc
Contact: Phil Sneiderman
Johns Hopkins University