Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Phytochemicals may protect cartilage, prevent pain in joints


Phase 2 enzyme inducers appear to stop harmful inflammation

Johns Hopkins researchers have discovered that plant-derived compounds known for their ability to protect tissue also appear to block the activity of an enzyme that triggers inflammation in joints. Their findings, based on experiments with human cells in a lab, could lead to new arthritis treatments and better methods of making artificial cartilage.

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 inducers to a dish containing the chondrocyte cells that are crucial to maintaining healthy joints. 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 results were surprising. "The beneficial phase 2 enzymes somehow seemed to prevent the activation of the inflammatory COX-2 enzyme," said Zachary R. Healy, a doctoral student in Konstantopoulos’ lab and lead author of the journal paper. "The phase 2 enzymes inhibited the inflammation and the apoptosis -- the cellular suicide we’d observed."

Some prescription drugs like Vioxx keep COX-2 enzyme at bay by temporarily blocking its ability to send the biochemical signals that set off pain and inflammation. When the medication is stopped, however, the stockpiled COX-2 enzyme can resume its damaging ways. Unlike these traditional pain killers, Healy said, the phase 2 enzyme inducers seemed to stop the increasing activity of 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."

Although these experiments appeared to be the first to determine how phase 2 enzyme inducers affect chondrocytes, these compounds have been studied extensively by researchers at the Johns Hopkins School of Medicine. Paul Talalay, the medical school’s John Jacob Abel Distinguished Service Professor of Pharmacology, 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. These phytochemicals can be found in cruciferous plants, including broccoli.

Talalay provided one of the phase 2 inducers used in Healy’s experiments. "This was 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," Talalay said. "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."

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 revitalize 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.

"More research is needed," said Konstantopoulos, who directed and supervised the experiments. "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."

Phil Sneiderman | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>