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."
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!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy