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 Portable finger-probe device can successfully measure liver function in potential organ donors
29.05.2015 | University of California - Los Angeles Health Sciences

nachricht Project start: New active substance targeting dreaded hospital pathogens
29.05.2015 | Deutsches Zentrum für Infektionsforschung

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: Lasers are the key to mastering challenges in lightweight construction

Many joining and cutting processes are possible only with lasers. New technologies make it possible to manufacture metal components with hollow structures that are significantly lighter and yet just as stable as solid components. In addition, lasers can be used to combine various lightweight construction materials and steels with each other. The Fraunhofer Institute for Laser Technology ILT in Aachen is presenting a range of such solutions at the LASER World of Photonics trade fair from June 22 to 25, 2015 in Munich, Germany, (Hall A3, Stand 121).

Lightweight construction materials are popular: aluminum is used in the bodywork of cars, for example, and aircraft fuselages already consist in large part of...

Im Focus: Solid-state photonics goes extreme ultraviolet

Using ultrashort laser pulses, scientists in Max Planck Institute of Quantum Optics have demonstrated the emission of extreme ultraviolet radiation from thin dielectric films and have investigated the underlying mechanisms.

In 1961, only shortly after the invention of the first laser, scientists exposed silicon dioxide crystals (also known as quartz) to an intense ruby laser to...

Im Focus: Advance in regenerative medicine

The only professorship in Germany to date, one master's programme, one laboratory with worldwide unique equipment and the corresponding research results: The University of Würzburg is leading in the field of biofabrication.

Paul Dalton is presently the only professor of biofabrication in Germany. About a year ago, the Australian researcher relocated to the Würzburg department for...

Im Focus: Basel Physicists Develop Efficient Method of Signal Transmission from Nanocomponents

Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.

Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...

Im Focus: IoT-based Advanced Automobile Parking Navigation System

Development and implementation of an advanced automobile parking navigation platform for parking services

To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International symposium: trends in spatial analysis and modelling for a more sustainable land use

20.05.2015 | Event News

15th conference of the International Association of Colloid and Interface Scientists

18.05.2015 | Event News

EHFG 2015: Securing health in Europe. Balancing priorities, sharing responsibilities

12.05.2015 | Event News

 
Latest News

Quasi-sexual gene transfer drives genetic diversity of hot spring bacteria

29.05.2015 | Life Sciences

First Eastern Pacific tropical depression runs ahead of dawn

29.05.2015 | Earth Sciences

Donuts, math, and superdense teleportation of quantum information

29.05.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>