Featured Research

from universities, journals, and other organizations

Hearing loss study reveals role of bone hardness in tissue function

Date:
November 18, 2010
Source:
University of California - San Francisco
Summary:
Scientists are reporting the first direct evidence that a subtle change in the physical properties of a tissue can affect its function.

The polar bear's ear bone is believed to be the hardest in its body, possibly helping the animal hear underwater. The finding has immediate implications for understanding several rare hearing disorders, they said, and ultimately could offer insight into such conditions as osteoporosis, arthritis, cardiovascular disease and cancer.
Credit: iStockphoto

Scientists are reporting the first direct evidence that a subtle change in the physical properties of a tissue can affect its function. The finding has immediate implications for understanding several rare hearing disorders, they said, and ultimately could offer insight into such conditions as osteoporosis, arthritis, cardiovascular disease and cancer.

In their study, the scientists discovered that blocking the function of a particular molecule in the ear bone of mice decreased the hardness of the bone, causing hearing loss. Reactivating the molecule restored the bone's hardness -- and the animals' hearing.

The research likely explains the previously unknown cause of hearing loss in the human disease cleidocranial dysplasia, a genetic bone syndrome,said co-author Lawrence Lustig, MD, UCSF professor of otolaryngology, and may explain hearing loss associated with some other bone diseases.

More broadly, the finding reveals the molecular pathway that regulates the physical properties of extracellular matrix -- the interlocking mesh of molecules between cells -- in the ear's cochlear bone. The matrix is responsible for the hardness of human tissues, ranging from stiff bone and enamel to compliant brain and skin.

Perhaps most intriguing is the discovery that variations in the physical properties of extracellular matrix affect tissue function. This finding should lead to insights into abnormal matrix properties in the tissues of diseases throughout the body, the researchers said, including osteoporosis and arthritis.

The polar bear's ear bone is believed to be the hardest in its body, possibly helping the animal hear under water.

"Our finding demonstrates that establishing and maintaining the proper calibration of physical properties is essential for healthy tissue function," said the senior author of the study, Tamara Alliston, PhD, assistant professor of orthopaedic surgery and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Scientists have known that physical cues, such as extracellular matrix stiffness, direct the differentiation of stem cells into specific cell types, such as heart, liver and brain cells. They also have known that disruption of these cues underlies a wide range of diseases, such as osteoarthritis, cardiovascular disease and cancer.

However, they have not known the molecular mechanisms that establish the physical properties of extracellular matrix, nor the link between these properties and tissue function.

In the current study, recently reported in EMBO (online Sept. 17, 2010), the team, led by Jolie L. Chang, MD, a resident in the UCSF Department of Otolaryngology and Head and Neck Surgery, set out to investigate the mechanisms involved.

Earlier studies, conducted at UCSF, showed that a molecule known as transforming growth factor beta (TGF-β) regulates the turnover of bone cells known as osteoblasts, by inhibiting a molecule known as Runx2. Disrupting TGF-β's regulation of Runx2 causes dysplastic clavicles and open cranial sutures.

These skeletal deformities, seen in the human genetic bone disease cleidocranial dysplasia, result from a defective copy of the Runx2 gene. Patients with CCD experience "sensorineural" hearing loss -- caused by damage to the cochlear bone or nerve damage.

Given these conditions, the teams used two mouse models of CCD to study the regulation and role of bone matrix properties in the cochlear bone.

They focused on this bone in part because of anecdotal evidence in patients, and research in whales, flamingos and polar bears, indicating that the bone is the hardest in the body, possibly helping the animals hear under water. The required stiffness, the team suspected, likely would be precisely calibrated.

They first conducted a nanoscale analysis of several mouse bones in the head and ear, establishing that the cochlea bone was by far the stiffest.

Then, in what they considered a major insight, they discovered that TGF-β regulates Runx2 to establish the physical property of the extracellular matrix of the cochlea bone. "This told us," said Chang, "that Runx2 -- a key transcriptional regulator that helps the cell selects its cell fate -- also controls the physical properties of the matrix."

Finally, by manipulating Runx2 activity through TGF-β, the team determined that the physical quality of the bone matrix affects hearing.

Now, the team is investigating the molecules "downstream" of Runx2, to gain further insight into the mechanism regulating the physical properties of bone. They also are studying if these mechanisms define the stiffness of matrices in other skeletal tissues.

"We want to see if TGF-β targets the cartilage transcription factor to make cartilage more or less stiff," Alliston said. "We think that the stiffness is degraded in arthritis and that this further disrupts chondrocyte cells, exacerbating the disease."

Other co-authors of the study are Delia S. Brauer, Jacob Johns, Carol Chen, Omar Akil, Emily N. Chin, Kristen Butcher, Richard A. Schneider, Anil Lalwani, Rik Derynck, Grayson W. Marshall, and Sally J. Marshall, of UCSF, Guive Balooch, at the time a postdoctoral fellow in the lab of co-author Robert O. Ritchie, of UC Lawrence Berkeley National Laboratories, Mary Beth Humphrey, of University of Oklahoma Health Science Center, and Alexandra E Porter, of Imperial College London.

The study was funded primarily by the National Institutes of Health, the Deafness Research Foundation, The Arthritis Foundation, UCSF School of Dentistry Creativity Fund, Arthritis Foundation, Deafness Research Foundation and Department of Energy.


Story Source:

The above story is based on materials provided by University of California - San Francisco. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jolie L Chang, Delia S Brauer, Jacob Johnson, Carol G Chen, Omar Akil, Guive Balooch, Mary Beth Humphrey, Emily N Chin, Alexandra E Porter, Kristin Butcher, Robert O Ritchie, Richard A Schneider, Anil Lalwani, Rik Derynck, Grayson W Marshall, Sally J Marshall, Lawrence Lustig, Tamara Alliston. Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-β and Runx2 in bone is required for hearing. EMBO reports, 2010; 11 (10): 765 DOI: 10.1038/embor.2010.135

Cite This Page:

University of California - San Francisco. "Hearing loss study reveals role of bone hardness in tissue function." ScienceDaily. ScienceDaily, 18 November 2010. <www.sciencedaily.com/releases/2010/11/101117141518.htm>.
University of California - San Francisco. (2010, November 18). Hearing loss study reveals role of bone hardness in tissue function. ScienceDaily. Retrieved August 29, 2014 from www.sciencedaily.com/releases/2010/11/101117141518.htm
University of California - San Francisco. "Hearing loss study reveals role of bone hardness in tissue function." ScienceDaily. www.sciencedaily.com/releases/2010/11/101117141518.htm (accessed August 29, 2014).

Share This




More Health & Medicine News

Friday, August 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. Video provided by Newsy
Powered by NewsLook.com
How A 'Rule Of Thumb' Could Slow Down Drinking

How A 'Rule Of Thumb' Could Slow Down Drinking

Newsy (Aug. 28, 2014) A study suggests people who follow a "rule of thumb" when pouring wine dispense less than those who don't have a particular amount in mind. Video provided by Newsy
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:
from the past week

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