Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Osteoporosis – new approach to treatment

07.01.2014
All over the world, researchers are working on new treatments for osteoporosis.

One potential target is a protein whose structures have now been decoded in detail by scientists from the University of Würzburg. The scientific journal Plos One covers their work in its latest issue.

One in three women and one in five men in the world over the age of 50 currently have excessively low bone density according to the International Osteoporosis Foundation. They therefore carry a significantly increased risk of suffering a bone fracture. The pathological decrease in the density of bone substance, also known as osteoporosis, often develops unnoticed. In healthy people, bone-building and bone-degrading processes occur in equilibrium, whereas degradation predominates in osteoporosis patients.

Sights set on the protein sclerostin

It is no wonder that scientists and pharmaceutical companies are working hard to develop new treatments for osteoporosis. One possible target is the protein sclerostin, which plays a pivotal role in what happens inside bones. “Sclerostin inhibits an important signaling pathway found in bone cells,” explains Professor Thomas Müller. The structural biologist from the Julius von Sachs Institute at the University of Würzburg has spent a long time working with this protein. In 2009, for example, he managed to decode its three-dimensional structure.

Müller was able to show that the protein is composed of three loops that emanate from a central knot. The first and third loops together form a defined structure, while the second loop is highly flexible. “The latter region in particular appears to be primarily responsible for the bone growth inhibitory effect,” says Müller.

Sclerostin inhibits bone growth

Sclerostin acts on the so-called Wnt signaling pathway in the body. This pathway plays a major role in ensuring that bone tissue remains stable. “Wnt proteins form a complex with two types of receptor at the cell surface; this then activates genes that are important for bone growth,” explains Müller. Sclerostin intervenes in this process and, in so doing, prevents activation of the Wnt signaling pathway, thereby generally inhibiting bone growth. “So, if we can block sclerostin using antibodies, for example, it will be possible to restore bone density even in already advanced osteoporosis,” says the scientist.

Now Thomas Müller and his team have succeeded in determining the structures in the sclerostin loop structure that are important for binding the protein to its receptor. Their achievement is reported on in the latest issue of the scientific journal Plos One. In addition, the team has shown that a change to the central knot also inhibits sclerostin. “Our studies reveal that the architecture of sclerostin is also important to the biological activity of the protein,” says Müller.

Building on these results, the scientists have already been able to develop an antibody that neutralizes sclerostin in collaboration with the company AbD Serotec. Its impact on bone growth is currently being examined.

Also helpful with excessive bone growth

This new knowledge concerning the way in which sclerostin works is not just useful for developing a treatment for osteoporosis. It is also conceivable that it may be helpful in the reverse direction, so to speak, namely for treating the bone diseases sclerosteosis and Van Buchem’s syndrome. “People afflicted by these very rare hereditary diseases form too little sclerostin or none at all and therefore suffer from excessive bone growth,” says Müller. In these patients, the bone mass grows so much that it wreaks nerve damage. Since the skull is also affected, loss of sight and hearing are common consequences in the absence of surgery; in extreme cases, excessive intracranial pressure can even lead to death.

With the new findings that show which areas of sclerostin are responsible for its effect and how these must be structured, scientists can now also design peptides that have a sclerostin-like effect, explains Müller. A “minimized” peptide-based sclerostin could represent a new, non-surgical treatment option for sclerosteosis and Van Buchem patients that would significantly improve their quality of life.

Mutational Analysis of Sclerostin Shows Importance of the Flexible Loop and the Cystine-Knot for Wnt-Signaling Inhibition. Verena Boschert, Maarten van Dinther, Stella Weidauer, Katharina van Pee, Eva-Maria Muth, Peter ten Dijke, Thomas D. Mueller. doi:10.1371/journal.pone.0081710

Contact

Prof. Dr. Thomas Müller,
T: +49 (0)931 31-89207, mueller@botanik.uni-wuerzburg.de

Gunnar Bartsch | idw
Further information:
http://www.uni-wuerzburg.de

More articles from Health and Medicine:

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

nachricht Alzheimer’s: Cellular Mechanism Provides Explanation Model for Declining Memory Performance
21.09.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

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: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>