Notch Signaling and Neurodegenerative Disc Disease

Notch proteins play a role in stimulating growth of a variety of cells.  This includes the proliferation of stem cells.

In this study the investigators link hypoxia to notch signaling and if notch plays a role in intervertebral disc cell proliferation.

This publications also references use of our Notch3 antibody.

Akihiko Hiyama, Renata Skubutyte, Dessislava Markova, D. Greg Anderson, Sanjay Yadla, Daisuke Sakai, Joji Mochida, Todd J. Albert, Irving M. Shapiro, Makarand V. Risbud. Hypoxia activates notch signaling pathway in cells of the intervertebral disc: Implications in degenerative disc disease. DOI: 10.1002/art.30246. Copyright © 2011 by the American College of Rheumatology.
Results: Nucleus pulposus (NP) and annulus fibrosus (AF) cells expressed components of the notch signaling pathway. Notch2 expression was higher than the other notch receptors in both AF and NP. In both tissues, hypoxia increased notch1 and notch4 mRNA expression. In the AF, expression of the notch ligand, jagged1 was induced by hypoxia; in both the tissues, jagged2 expression was hypoxia-sensitive. To investigate if hypoxia promoted notch signaling, we measured the activity of twonotch responsive luciferase reporters, 12xCSL and CBF-1. L685458, a notch signaling inhibitor blocked hypoxic induction of both the reporter activities. We then investigated regulation of expression of the notch target gene Hes1. Hes1 expression was induced in hypoxia while co-expression of notch-ICD increased Hes1 promoter activity. Moreover, inhibition of notch signaling blocked disc cell proliferation. Finally, analysis of human discal tissues showed that there was increased expression of notch signaling proteins in the degenerate state.

Conclusion: In disc cells, hypoxia promotes expression of notch signaling proteins. Notch signaling is important to maintain proliferation of disc cells and hence offers a therapeutic target to restore cell number during degenerative disc disease.

Hope for sufferers of degenerative disease disc disease.