Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lack of specific collagen type leads to osteoarthritis

21.02.2005


Duke University Medical Center researchers have found that joints whose cartilage lacks a specific type of collagen will develop osteoarthritis – the so-called "wear-and-tear" form of the disease – at a greatly accelerated rate.



The results of their experiments with mice provide new insights that could lead to potential treatments for a disease that afflicts more than 40 million Americans, said the researchers.

The researchers found that mice lacking the gene that controls the production of type VI collagen developed osteoarthritis at a rate more than five times greater than mice with a functioning gene. Collagen is a ubiquitous protein found throughout the body in connective tissue, muscle, cartilage and bone. To date, 27 different types have been identified.


To examine structures within the cartilage of mouse joints, Leonidas Alexopoulos, Ph.D., developed a novel "micro-vacuuming" technique. With this device, Alexopoulos extracted key structures within the cartilage of mouse hip joints, which are the size of the ball in a ball-point pen, and analyzed how they responded to the stresses of everyday life.

Alexopoulos presented the results of the Duke study Feb. 20, 2005, at the 51th annual scientific meeting of the Orthopedic Research Society in Washington, D.C. Alexopoulos, now a post-doctoral fellow at the Massachusetts Institute of Technology, conducted the research in the laboratory of Farshid Guilak, Ph.D., director of orthopedic research and senior member of the Duke team. The study was funded by the National Institutes of Health.

The researchers focused their attention on the narrow region of tissue that surrounds the cartilage cells on the surface of joints and is known as the pericellular matrix (PCM). Together with cartilage cells known as chondrocytes, collagen types II, VI and IX, and other proteins, the PCM forms a structure called a chondron, which is believed to provide a "buffer" zone between the cells and the remainder of the cartilage tissue.

"The interesting thing is that type VI collagen occurs nowhere else in the cartilage but the PCM, and no one really understood why," Alexopoulos explained. "When we analyzed the PCM of mice unable to produce type VI collagen, we found that the chondrons in these mice were much softer and the joints did not respond well to mechanical pressures. The joint looked as if it osteoarthritis had developed.

"It appears now that the type VI collagen acts like a scaffold that provides structure and stiffness to the PCM," Alexopoulos continued. "With this model for osteoarthritis, we have a better understanding of how changes in the mechanical forces on the cells may lead to degeneration of the cartilage."

For their experiments, the team compared how chondrons changed over time in three different groups of mice: one group had functioning type VI collagen genes, while the two other groups were strains of "knockout" mice developed by Paolo Bonaldo, University of Padova, Italy. One group of mice had both parents with the type VI collagen gene knocked out, while the other group had only one parent without the gene. After six months, the researchers removed chondrons to determine how they responded.

"We found significant osteoarthritic and developmental differences among the three groups," Alexopoulos said. Specifically, 73 percent of the mice with two knock-out parents showed evidence of mild to severe osteoarthritis. This compared to 40 percent for mice with one knock-out parent and 13 percent for the control mice.

"These findings represent an important advance in our understanding of osteoarthritis," Guilak said. "The study provides direct evidence of the role of type VI collagen in the biomechanical properties of the PCM. While the mechanism behind the accelerated development of osteoarthritis is not yet clear, it suggests that the lack of type VI collagen negatively impacts the ability of the cartilage to respond properly to the mechanical stresses and pressures on the joint."

The experiments would not have been possible without the custom-built "microaspirator," which could extract individual, intact chondrons. Other methods of isolating chondrons, which either involve dissolving surrounding tissues with harsh enzymes or grinding the cartilage in pieces, typically yield damaged chondrons, Alexopoulos said.

"Using a tiny syringe, I was able to go across the surface of the cartilage and vacuum up the chondrons without damaging them," Alexopoulos said. "The chondrons literally popped out of the cartilage and into the syringe. From that point, it was easy to analyze their structure."

It is estimated that more than 70 percent of Americans over the age of 65 show some signs of osteoarthritis, which is characterized by the slow degeneration of the buffering layer of cartilage within joints. The other major form of arthritis, rheumatoid arthritis, occurs when the body’s immune system attacks the linings of joints.

Guilak currently leads of group of clinicians and investigators from Duke and the Durham VA Medical Center who are carrying out a broad range of basic and clinical research into better understanding and treating osteoarthritis.

Richard Merritt | EurekAlert!
Further information:
http://www.mc.duke.edu

More articles from Health and Medicine:

nachricht Spanish scientists create a 3-D bioprinter to print human skin
24.01.2017 | Carlos III University of Madrid

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists spin artificial silk from whey protein

X-ray study throws light on key process for production

A Swedish-German team of researchers has cleared up a key process for the artificial production of silk. With the help of the intense X-rays from DESY's...

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Breaking the optical bandwidth record of stable pulsed lasers

24.01.2017 | Physics and Astronomy

Choreographing the microRNA-target dance

24.01.2017 | Life Sciences

Spanish scientists create a 3-D bioprinter to print human skin

24.01.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>