Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis

Authors

Qin Bian, Johns Hopkins University
Lei Ma, Johns Hopkins University
Amit Jain, Johns Hopkins University
Janet L. Crane, Johns Hopkins University
Khaled Kebaish, Johns Hopkins University
Mei Wan, Johns Hopkins University
Zhengdong Zhang, Columbia University in the City of New York
X. Edward Guo, Columbia University in the City of New York
Paul D. Sponseller, Johns Hopkins University
Cheryle A. Séguin, Western University
Lee H. Riley, Johns Hopkins University
Yongjun Wang, Shanghai University of Traditional Chinese Medicine
Xu Cao, Johns Hopkins University

Document Type

Article

Publication Date

3-21-2017

Journal

Bone Research

Volume

5

URL with Digital Object Identifier

10.1038/boneres.2017.8

Abstract

Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal (NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αv β6-mediated activation of transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease (DDD). Knockout of TGFβ type II receptor (TβRII) or integrin α v in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and α v β 6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.

Notes

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The article was originally published as:

Bian, Q., Ma, L., Jain, A. et al. Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis. Bone Res 5, 17008 (2017). https://doi.org/10.1038/boneres.2017.8

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.