IBMS BoneKEy | Perspective

TGFβ and Runx2 calibration of bone extracellular matrix quality for tissue-specific function

Tamara Alliston
Jolie Chang

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DOI:10.1138/20110525

Abstract

Each extracellular matrix (ECM) throughout the body has specific physical properties. However, very little is known about how tissue-specific physical properties such as ECM elastic modulus are established or maintained. The fine regulation of ECM elastic modulus is particularly apparent in the skeleton where the material properties of bone are anatomically distinct, developmentally regulated, and evolutionarily conserved. Consequently, the skeleton has served as an excellent model system in which to study mechanisms that define tissue-specific material properties and couple them to tissue-specific function. Using this approach, we found that the uniquely hard ECM of cochlear bone is regulated through the activity of the lineage-specific transcription factor Runx2 via the same TGFβ-dependent pathway that controls osteoblast differentiation and ECM protein expression. Furthermore, this regulation is essential for tissue-specific function in hearing. While the mechanisms by which TGFβ regulates ECM material properties are currently most well-defined, they likely serve as an example for other signaling pathways. It is possible that similar mechanisms are active in non-skeletal tissues, such that growth factors target lineage-specific transcription factors to define ECM material properties of other tissues. By examining the role of bone quality in hearing, this article will explore mechanisms by which tissue-specific material properties are established and linked to normal tissue function.

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