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 Nanotubes are beacons in cancer-imaging technique
23.05.2016 | Rice University

nachricht More light on cancer
20.05.2016 | Lomonosov Moscow State University

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: Worldwide Success of Tyrolean Wastewater Treatment Technology

A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.

The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

11 million Euros for research into magnetic field sensors for medical diagnostics

27.05.2016 | Awards Funding

Fungi – a promising source of chemical diversity

27.05.2016 | Life Sciences

New Model of T Cell Activation

27.05.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>