Document Type

Article

Publication Date

3-20-2018

Comments

This article has been peer reviewed. It is the author’s final published version in Scientific Reports, Volume 8, Issue 1, March 2018, Article number 4856.

The published version is available at https://doi.org/10.1038/s41598-018-23196-7 . Copyright © Silagi et al.

Abstract

The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis. NP, but not annulus fibrosus or end-plate cells, robustly expressed CAIII protein in skeletally mature animals. Although CAIII expression was hypoxia-inducible, we did not observe binding of HIF-1α to select hypoxia-responsive-elements on Car3 promoter using genomic chromatin-immunoprecipitation. Similarly, analysis of discs from NP-specific HIF-1α null mice suggested that CAIII expression was independent of HIF-1α. Noteworthy, silencing CAIII in NP cells had no effect on extracellular acidification rate, CO

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

Language

English

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