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- Title
Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-β and Runx2 in bone is required for hearing.
- Authors
Chang, Jolie L; Brauer, Delia S; Johnson, Jacob; Chen, Carol G; Akil, Omar; Balooch, Guive; Humphrey, Mary Beth; Chin, Emily N; Porter, Alexandra E; Butcher, Kristin; Ritchie, Robert O; Schneider, Richard A; Lalwani, Anil; Derynck, Rik; Marshall, Grayson W; Marshall, Sally J; Lustig, Lawrence; Alliston, Tamara
- Abstract
Physical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-β (TGFβ)-responsive pathway that controls osteoblast differentiation. Deregulated TGFβ or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2+/⁻ mice, inhibition of TGFβ signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue function.
- Publication
EMBO reports, 2010, Vol 11, Issue 10, p765
- ISSN
1469-3178
- Publication type
Journal Article
- DOI
10.1038/embor.2010.135