Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A key signaling molecule in osteoarthritis is identified

04.01.2005


Using naturally-occurring mutant mice with a defective collagen gene, scientists at Harvard have identified a signaling molecule involved in one of the most common causes of disability among the elderly in the United States, osteoarthritis. Inhibitors of this molecule’s signaling may eventually be used to slow down the progression of the disease, thus helping to relieve chronic pain in a large segment of the population.



The research appears as the "Paper of the Week" in the January 7 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

It is estimated that all individuals over the age of 75 are afflicted with osteoarthritis. The disease, which is actually a group of overlapping but distinct diseases with similar clinical outcomes, is most common form of arthritis. It is characterized by the breakdown of cartilage, which cushions the ends of bones, in the joints of the knees, hips, feet and back. This cartilage breakdown causes the bones to rub against each other, resulting in pain and loss of movement.


"The earliest indication of the disease is a gradual loss of large molecules called proteoglycans from the surface of the joint cartilage," notes Dr. Yefu Li of the Harvard School of Dental Medicine. "This results in a decrease in the mechanical strength of cartilage. At the same time, cells proliferate and form clusters. Then cracks in the cartilage gradually develop and the cracks are filled with a fibrous tissue; this is considered to be the result of unsuccessful attempts by the cartilage cells to repair the cracks. Finally, bony structures, called osteophytes, are formed at the periphery of the joint. The end result is loss of joint function."

Although the causes of osteoarthritis are diverse, mutations in two types of collagens, type IX and XI, have been linked to early-onset osteoarthritis. However, the link between the collagen mutations and the pathogenesis of osteoarthritis is not clear.

To further elucidate the relationship between collagen mutations and the pathogenesis of osteoarthritis, Dr. Yefu Li and his colleagues at Harvard studied mice with a mutation in type XI collagen. These mice exhibit age-related osteoarthritis–like changes in various joints, which is similar to what is seen in humans.

"Information about molecular and cellular events during the initiation and progression of osteoarthritis is limited since current research efforts are mostly focused on either risk factors for the disease or biochemical events in cartilages of joints at later stages of the disease," explains Dr. Li. "However, the similar clinical outcomes in different forms of osteoarthritis suggest that a common molecular sequence of events is responsible for the progression of the disease. Identification of molecules that are critical in this sequence may not only help us to understand the disease better, but may also provide information for the design of new therapeutic strategies for the treatment of osteoarthritis."

Dr. Li and his colleagues found that the mutant mice had increased amounts of the protein discoidin domain receptor 2 (DDR2) in the articular cartilage chondrocytes (cartilage cells) of their knee joints. "DDR2 is a signaling receptor on cell surfaces that binds to collagen fibrils outside the cells," explains Dr. Li. "The normal function of DDR2 is largely unknown. One report demonstrates that the lack of DDR2 results in dwarfism in mice, probably due to decreased proliferation of cartilage cells during bone growth."

The increase in DDR2 caused an increase in the expression of matrix metalloproteinase-13 (MMP-13), a protein that remodels the extracellular matrix by degrading major matrix components.

"Our study suggests that collagen binds to DDR2 and stimulates the production of an enzyme, MMP-13, that in turn degrades the cartilage," concludes Dr. Li. "Our study also identifies a signaling pathway in cartilage cells used by DDR2 to regulate the synthesis of MMP-13. Our results bring us one step closer to identifying a possible early and common step in the development of different forms of osteoarthritis."

Dr. Li’s results suggest that inhibitors of DDR2 signaling may be useful as drugs to slow down osteoarthritis progression. This comes as good news in the wake of several drugs used to treat arthritic pain being linked to severe side effects.

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>