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.

H9-WA09 Derived Human Neural Progenitors and Neurons Pricing

Neuromics offers stable, potent and well characterized STEMEZ (TM) Human Neural Progenitor & Neuron Discovery Kits. These are derived from NIH registered human ES cell line H9 (WA09).

Details on the capabilities of these cells are detailed in a variety of publications. They work! As a result, I am trying to make it easier to justify using them when and where they are needed. In addition to having frequent updates on new references, methods and data, I want to offer the best pricing possible.

In researching pricing of cells derived from the same parental line and having similar characteristics, I noticed prices ranging from 995 to 2800 USD. Our pricing starts at 695 USD and we offer deeper discounting if required. I do not want price to be a barrier. Here's some sample data on these cells.

Images: Neural phenotypes derived from hN2 cell lines. (A) Phase contrast image of differentiated culture. (B) Network including post-mitotic motoneurons (HB9). (C) Cholinergic neuron. (D) Tuj-1 positive cells that are DAT-positive (dopamine transporter; closed arrow) and DAT-negative (open arrow). (E) Gabaergic neurons, inset illustrates GABA in axon, but not the dendrites (arrow).

G-protein Coupled Receptor Expression Patterns Are Altered as Human Embryonic Stem Details-From Poster Presented at Neuroscience 2008 by Dr. Steve Stice et al.
hN2 Cells-Electro Phys Data.

Related Products:

• All Stem Cell Research Reagents
• Primary Neurons and Astrocytes

I wish exciting and rewarding discoveries.

More on DOR

I am always delighted when we recieve positive feedback on one of our new reagents. It is even better when a researcher graciously shares images. I would like to thank Dr. Prof. Dr. Rapheal Sell of Freie Universität Berlin for sharing these excellent Immunofluorescence images:

Images: IF detection of delta-opioid receptors in tissue engineered human oral mucosa models using Delta Opioid Receptor 361-372. The tissues were frozen at -80°C, cut into 8 µm slices and fixed with formaldehyde solution. Blocking was performed with goat serum (dilutet 1:20 in PBS) for 30 minutes at RT. Primary antibody dilutions in PBS/BSA/Tween-20 were 1:500, 1:1000 and 1:1500, slides were incubated overnight at 4°C. Secondary (fluorescent) antibody was diluted 1:400, slides were incubated for 30 minutes at room temperature in the dark. Sections were mounted with antifading mounting medium DAPI (blue) and evaluated by fluorescent microscopy

Related Reagents:

Delta Opioid Receptor 3-17

Delta Opioid Receptor 358-372

All Opioid Receptor Antibodies          

Neurotransmission Research Antibodies-GPCRs, Ligand Gated Ion Channels, Biogenic Amines and more

Primary Neurons and Astrocytes-Primary human, rat and mouse neurons and astrocytes