Featured Research

from universities, journals, and other organizations

Gains made towards treatment of rare bone disease

Date:
February 20, 2013
Source:
McGill University
Summary:
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 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.

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.

Related Articles


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 Fundaηγo de Amparo ȧ Pesquisa do Estado de Sγo Paulo (Brasil).


Story Source:

The above story is based on materials provided by McGill University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nilana MT Barros, Betty Hoac, Raquel L Neves, William N Addison, Diego M Assis, Monzur Murshed, Adriana K Carmona, Marc D McKee. Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia. Journal of Bone and Mineral Research, 2013; 28 (3): 688 DOI: 10.1002/jbmr.1766

Cite This Page:

McGill University. "Gains made towards treatment of rare bone disease." ScienceDaily. ScienceDaily, 20 February 2013. <www.sciencedaily.com/releases/2013/02/130220123419.htm>.
McGill University. (2013, February 20). Gains made towards treatment of rare bone disease. ScienceDaily. Retrieved March 4, 2015 from www.sciencedaily.com/releases/2013/02/130220123419.htm
McGill University. "Gains made towards treatment of rare bone disease." ScienceDaily. www.sciencedaily.com/releases/2013/02/130220123419.htm (accessed March 4, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, March 4, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Adults Only Get The Flu Twice A Decade, Researchers Say

Adults Only Get The Flu Twice A Decade, Researchers Say

Newsy (Mar. 4, 2015) — Researchers found adults only get the flu about once every five years. Scientists analyzed how a person&apos;s immunity builds up over time as well. Video provided by Newsy
Powered by NewsLook.com
New Hormone Could Protect Against Diabetes And Weight Gain

New Hormone Could Protect Against Diabetes And Weight Gain

Newsy (Mar. 4, 2015) — A newly discovered hormone mimics the effects of exercise, protecting against diabetes and weight gain. Video provided by Newsy
Powered by NewsLook.com
Mount Everest Has a Poop Problem

Mount Everest Has a Poop Problem

Buzz60 (Mar. 4, 2015) — With no bathrooms to use, climbers of Mount Everest have been leaving human waste on the mountain for years, and it&apos;s becoming a health issue. Mike Janela (@mikejanela) has more. Video provided by Buzz60
Powered by NewsLook.com
The Best Tips to 'Skinny' Your Home

The Best Tips to 'Skinny' Your Home

Buzz60 (Mar. 4, 2015) — If you&apos;re looking to reach your health goals this season, there are a few simple tips to help you spring clean your space and improve your nutrition. Krystin Goodwin (@krystingoodwin) has the skinny on keeping a healthy home. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins