Acidosis Is a Key Regulator of Osteoblast Ecto-Nucleotidase Pyrophosphatase/Phosphodiesterase 1 (NPP1) Expression and Activity

Orriss, I R; Key, M L; Hajjawi, M O R; Millan, J L; Arnett, T R

Abstract

Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (Pi) to pyrophosphate (PPi) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both Pi and PPi, a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto‐nucleotidases. This study investigated the expression and activity of ecto‐nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto‐nucleotidases including NTPdase 1–6 (ecto‐nucleoside triphosphate diphosphohydrolase) and NPP1‐3 (ecto‐nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1 > NTPdase 4 > NTPdase 6 > NTPdase 5 > alkaline phosphatase > ecto‐5‐nucleotidase > Enpp3 > NTPdase 1 > NTPdase 3 > Enpp2 > NTPdase 2. Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8‐fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto‐nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (P 

Citation

Orriss, I. R., Key, M. L., Hajjawi, M. O. R., Millan, J. L., & Arnett, T. R. (2015). Acidosis Is a Key Regulator of Osteoblast Ecto-Nucleotidase Pyrophosphatase/Phosphodiesterase 1 (NPP1) Expression and Activity. Journal of Cellular Physiology, 230(12), 3049-3056. https://doi.org/10.1002/jcp.25041

• Journal Article Type: Article
• Acceptance Date: May 7, 2015
• Publication Date: Aug 24, 2015
• Deposit Date: Oct 20, 2015
• Publicly Available Date: Nov 21, 2020
• Journal: Journal of Cellular Physiology
• Print ISSN: 0021-9541
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 230
• Issue: 12
• Pages: 3049-3056
• DOI: https://doi.org/10.1002/jcp.25041
• Public URL: https://rvc-repository.worktribe.com/output/1399898