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 FAU researchers demonstrate that an oxygen sensor in the body reduces inflammation
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht 'Icebreaker' protein opens genome for t cell development, Penn researchers find
21.02.2018 | University of Pennsylvania School of Medicine

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: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

The RWI/ISL-Container Throughput Index started off well in 2018

22.02.2018 | Business and Finance

FAU researchers demonstrate that an oxygen sensor in the body reduces inflammation

22.02.2018 | Health and Medicine

Histology in 3D: new staining method enables Nano-CT imaging of tissue samples

22.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>