期刊
EMBO REPORTS
卷 11, 期 10, 页码 765-771出版社
WILEY
DOI: 10.1038/embor.2010.135
关键词
elastic modulus; Runx2; hearing; TGF-beta; bone quality
资金
- National Institute of Dental and Craniofacial Research [R03 DE16868, R01 DE019284, T32 DE007306, R01 DE016402, P01 DE09859]
- Howard Hughes Medical Institute
- Triological Society
- Hearing Research Institute
- National Institutes of Health National Center for Research Resources
- National Institute on Deafness and Other Communication Disorders [K08 DC00189]
- University of California, San Francisco School of Dentistry
- Arthritis Foundation
- Deafness Research Foundation
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-beta (TGF beta)-responsive pathway that controls osteoblast differentiation. Deregulated TGF beta 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 TGF beta 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据