Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team led by Scripps Research scientists discovers body's own molecular protection against arthritis

19.05.2010
The results may lead to new approach to therapies for joint disease

An international team of scientists from The Scripps Research Institute in California and the National Research Institute for Child Health and Development in Japan has discovered that a natural molecule in the body counters the progression of osteoarthritis. The findings could one day lead to new therapies for some common diseases of aging.

The study was published in an advanced, online issue of the journal Genes & Development on May 13, 2010, and will be featured as the cover story of the June 1 print edition of the journal.

The molecule the team studied, microRNA 140 (miR-140), is part of a recently discovered category of genetic molecules—"microRNAs" or "non-coding RNAs" which do not code for proteins, yet often play a vital role in gene expression.

"This is the first report showing the critical role of a specific non-coding RNA in bone development," said Hiroshi Asahara, M.D., Ph.D., associate professor of molecular and experimental medicine at Scripps Research. "Moreover, surprisingly, we observed that microRNA 140 acts against arthritis progression. This is among the first evidence that non-coding RNA plays a key role in age-dependent diseases."

"This finding may lead to a new therapeutic strategy for osteoarthritis," said Shigeru Miyaki, senior research associate in the Asahara lab and first author of the paper with Tempei Sato of the National Research Institute for Child Health and Development, "as well as for conditions that share a similar mechanism, such as spinal disc degeneration."

Broad Impact

Even in comparison with other diseases of aging, osteoarthritis has a remarkably broad impact. Currently affecting about 15 to 20 million Americans, osteoarthritis is the most common joint disorder and is expected to increase by 50 percent over the next two decades with the aging of the population. With no effective treatments, current management strategies for osteoarthritis focus on reducing pain and inflammation.

Osteoarthritis, also known as degenerative arthritis, is a disease that affects joint cartilage, the major weight-bearing "cushion" in joints. The disease results from a combination of wear and tear on cartilage and underlying age-related changes that causes cartilage to deteriorate. Joint trauma can also play a role. Osteoarthritis commonly affects the hands, spine, hips, and knees.

Asahara and other members his laboratory were interested in the question of why some people's joints age normally, while others' spiral toward disease.

The scientists suspected that microRNA could play a role. Once thought of as mere genetic helpers, microRNAs are now known to prevent proteins from being produced by messenger RNA, thus acting as an important layer of regulation for biological processes.

"Recent research findings indicate that non-coding RNA should be involved in our development and in diseases," said Asahara, "but we know little about the role of the non-coding RNA for age-related adult disorders."

Breaking New Ground

The team's interest in one type of microRNA in particular, miR-140, was piqued by other work ongoing in the lab, which was published last year. In this study, the team made the observation that miR-140—which is only expressed in cartilage—was reduced in cartilage samples from osteoarthritis patients. This led the team to hypothesize that miR-140 is a regulator in osteoarthritis pathology.

To test this idea, the team tried for several years to make targeted "knockout" mouse models that lacked miR-140. They finally succeeded.

With models lacking miR-140, the scientists were able to figure out its effects. Since the animals lacking miR-140 were short in stature, the scientists concluded that miR-140 affected bone formation during development. The mutant mice were also particularly prone to developing osteoarthritis, suggesting that miR-140 retarded the disease. In contrast, the scientists found, transgenic mice that overexpressed miR-140 were resistant to developing the condition.

The team's findings fit in well with other recent research showing that an enzyme called Adamts-5 is necessary for osteoarthritis progression; miR-140 is known to regulate Adamts-5.

The team continues to investigate to learn more about the factors that control miR-140, the proteins it affects, and potential drugs that might influence its action.

In addition to Asahara, Miyaki, and Sato, authors of the paper "MicroRNA-140 plays dual roles in both cartilage development and homeostasis," are Atsushi Inoue, Yoshiaki Ito, Shigetoshi Yokoyama, Fuko Takemoto, Tomoyuki Nakasa, Satoshi Yamashita, Shuji Takada, and Hiroe Ueno-Kudo of the National Research Institute for Child Health and Development in Japan, Yoshio Kato of the National Institute of Advanced Industrial Science and Technology in Japan, and Shuhei Otsuki and Martin Lotz of Scripps Research.

U.S. sources of funding for this project included the National Institutes of Health, the Arthritis National Research Foundation, and the Arthritis Foundation. Japanese sources of funding included the Japanese Ministry of Health, Labor, and Welfare; the Genome Network Project; National Institute of Biomedical Innovation, Research on Child Health and Development; and The Japan Health Sciences Foundation.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

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

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>