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Hearing loss study reveals role of bone hardness in tissue function
Date:11/17/2010

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 di
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Contact: Jennifer O'Brien
jennifer.obrien@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert

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