eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2018   Volume No 36 – pages 1-14

Title: Transcriptional activation of ENPP1 by osterix in osteoblasts and osteocytes

Authors: MM Gao, QN Su, TZ Liang, JX Ma, MJ Stoddart, RG Richards, ZY Zhou, XN Zou

Address: Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology/Orthopaedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

E-mail: zxnong at

Abstract: Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the main source of extracellular pyrophosphate. Along with tissue-nonspecific alkaline phosphatase (TNAP), ENPP1 plays an important role in balancing bone mineralisation. Although well established in pre-osteoblasts, the regulating mechanisms of ENPP1 in osteoblasts and osteocytes remain largely unknown. Using bioinformatic methods, osterix (Osx), an essential transcription factor in osteoblast differentiation and osteocyte function, was found to have five predicted binding sites on the ENPP1 promoter. ENPP1 and Osx showed a similar expression profile both in vitro and in vivo. Over-expression of Osx in MC3T3-E1 and MLO-Y4 cells significantly up-regulated the expression of ENPP1 (p < 0.05). The consensus Sp1 sequences, located in the proximal ENPP1 promoter, were identified as Osx-regulating sites using promoter truncation experiments and chromatin immunoprecipitation (ChIP) assays. The p38-mitogen-activated protein kinase (MAPK) signalling pathway was demonstrated to be responsible for ENPP1 promoter activation by Osx. Runt-related transcription factor 2 (Runx2) was confirmed to have synergistic effects with Osx in activating ENPP1 promoter. Taken together, these results provided evidence of the regulating mechanisms of ENPP1 transcription in osteoblasts and osteocytes.

Key Words: Pyrophosphatase/phosphodiesterase 1, osterix, gene regulation, mineralisation, osteogenesis.

Publication date: July 25th 2018

Article download: Pages 1-14 (PDF file)

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