Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis

Qin Bian, Lei Ma, Amit Jain, Janet L. Crane, Khaled Kebaish, Mei Wan, Zhengdong Zhang, X. Edward Guo, Paul D. Sponseller, Cheryle A. Séguin, Lee H. Riley, Yongjun Wang, Xu Cao

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


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.

Original languageEnglish (US)
Article number17008
JournalBone Research
StatePublished - Mar 21 2017

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology


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