Phytochemicals may protect cartilage and prevent joint pain

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Phytochemicals may protect cartilage and prevent joint pain



Oct 12, 2005



Gandey

Baltimore, MD - Plant-derived compounds known for their ability to

protect tissue also appear to block the activity of an enzyme that

triggers inflammation in joints, new preliminary findings show. " More

research is needed, " senior author Dr Konstantinos Konstantopoulos

(s Hopkins University, Baltimore, MD) told reporters. " But these

discoveries could provide guidelines for designing an ideal

hydrodynamic environment in bioreactors for generating functional

cartilage as well as for the treatment of osteoarthritis. " The

results appear in the September 27, 2005 issue of the Proceedings of

the National Academy of Sciences [1].



" This is the first work done in applying these phytochemicals to

chondrocytes, which are constantly under the influence of forces

because of the way we move our joints, " Dr Talalay (s

Hopkins University) said to the press. In previous research, Talalay

has shown that phase 2 enzymes can detoxify certain cancer-causing

agents and damaging free radicals in tissue, including cells that

line blood vessels. He has isolated compounds in edible plants that

boost production of phase 2 enzymes. Talalay provided one of the

phase 2 inducers used in these new experiments. " The phase 2 inducers

seemed to counteract the effects of that stress by inhibiting the

expression of COX-2 enzyme. It's interesting to think that people may

be able to obtain this benefit through dietary components. "



This is the first work done in applying these phytochemicals to

chondrocytes, which are constantly under the influence of forces

because of the way we move our joints.



According to a news release, these latest findings came to light

while the researchers were studying the different ways cells in human

blood vessels and joints respond to pressure gradients generated from

liquid moving along their surface—a force known as shear stress. In

cells that line blood vessels, the reaction to shear stress is

beneficial and boosts phase 2 enzymes that may protect the cells from

cancer-causing chemicals and other toxic agents. But in joints, the

response to intense shear stress is potentially harmful and could

trigger an increase in the levels of COX-2 enzyme linked to

inflammation and pain, which suppress the activity of phase 2

enzymes, ultimately causing the death of chondrocytic cells.

The researchers, led by Zachary Healy, a doctoral student in

Konstantopoulos's lab, questioned what would happen, if strenuous

exercise or heavy muscle exertion can cause joints to increase the

levels of harmful COX-2 enzyme, if the vulnerable chondrocyte cells

in human joints were first exposed to the beneficial phase 2 enzymes.

To find out, the group obtained compounds that boost the activity of

helpful phase 2 enzymes and they added these phase 2 inducers to a

dish containing the chondrocyte cells crucial to maintaining healthy

joints. After 24 hours, they subjected the cells to a stress test

designed to mimic aspects of strenuous exercise on a joint. They also

exposed the cells to a hydrodynamic environment in a bioreactor

designed to generate artificial cartilage.







Cells undergo shear stress testing to mimic conditions within a human

joint (Photograph by Will Kirk)



The results, they say, were surprising. " The beneficial phase 2

enzymes somehow seemed to prevent the activation of the inflammatory

COX-2 enzyme, " Healy told reporters. " The phase 2 enzymes inhibited

the inflammation and the apoptosis—the cellular suicide we'd

observed. "

Healy pointed out that, unlike currently available COX-2 inhibitors,

which have a temporary effect, these phase 2 enzyme inducers seem to

stop the increasing activity of the COX-2 enzyme. " That means these

compounds could be useful as a preventive measure—perhaps before

strenuous exercise, " Healy said. " This has the potential for stopping

pain and inflammation before they start. "

In their paper, the researchers conclude that these findings

highlight the existing cross talk among COX-2 expression, reduced

antioxidant capacity, and increased apoptosis in sheared chondrocytic

cells—all earmarks of arthritis. " Reconstructing the biochemical

pathways regulating cartilage inflammation and chondrocyte apoptosis

in response to high shear stress may identify potential therapeutic

targets for controlling arthritic pathogenesis and progression and

may be useful in the design of bioreactors for cartilage culture. "



Source



Healy ZR, Lee NH, Gao X, et al. Divergent responses of chondrocytes

and endothelial cells to shear stress: Cross-talk among COX-2, the

phase 2 response, and apoptosis. Proc Natl Acad Sci 2005;

102:14010-14015.

http://www.jointandbone.org/viewArticle.do?primaryKey=576125