Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gains made towards treatment of rare bone disease

21.02.2013
Elusive substrate protein identified in the most common form of heritable rickets
Diagnosed in toddlers, X-linked hypophosphatemia (XLH) is the most common form of heritable rickets, in which soft bones bend and deform, and tooth abscesses develop because infections penetrate soft teeth that are not properly calcified. Researchers at McGill University and the Federal University of Sao Paulo have identified that osteopontin, a major bone and tooth substrate protein, plays a role in XLH. Their discovery may pave the way to effectively treating this rare disease.

The findings were made by the laboratories of Marc McKee, a professor in the Faculty of Dentistry and the Department of Anatomy and Cell Biology at McGill University, and of Nilana M.T. Barros, a professor at the Federal University of Sao Paulo. The team built upon previous research that had shown that mutations in the single gene PHEX are responsible for causing XLH. The results of this latest research by Drs. McKee and Barros will be published in the March issue of the Journal of Bone and Mineral Research.
“XLH is caused in part by renal phosphate wasting, which is the urinary loss from the body of phosphate, an important building block of bones and teeth, along with calcium.” says Prof. McKee. “In pursuing other factors that might contribute to XLH, we used a variety of research methods to show that PHEX enzymatic activity leads to an essentially complete degradation of osteopontin in bones.”

This loss of osteopontin, a known potent inhibitor of mineralization (or calcification) in the skeleton and dentition, normally allows bones and teeth to mineralize and thus harden to meet the biomechanical demands placed on them. In XLH patients lacking functional PHEX enzyme, osteopontin and some of its smaller potent inhibitory peptides are retained and accumulate within the bone. This prevents their hardening and leads to soft deformed bones such as bowed legs (or knock-knees) seen in toddlers.

While not life-threatening, this decreased mineralization of the skeleton (osteomalacia), along with the soft teeth, soon leads to a waddling gait, short stature, bone and muscle pain, weakness and spontaneous tooth abscesses.

The fact that these symptoms are only partially improved by the standard treatment with phosphate – which improves circulating phosphate levels – prompted the researchers to look for local factors within the bone that might be blocking mineralization in these patients.

“With this new identification of osteopontin as a substrate protein for PHEX,” says Professor Barros, “we can begin to develop an enzyme-replacement therapy to treat XLH patients who have nonfunctional PHEX, much as has been done using a different enzyme to treat another rare bone disease called hypophosphatasia.”

This research was jointly funded by the Canadian Institutes of Health Research (Canada) and Fundação de Amparo ȧ Pesquisa do Estado de São Paulo (Brasil).

Contact: Cynthia Lee
Organization: McGill University
Email: cynthia.lee@mcgill.ca
Office Phone: 514-398-6754

Cynthia Lee | EurekAlert!
Further information:
http://www.mcgill.ca

More articles from Health and Medicine:

nachricht How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

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: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>