Hypoxia mediates osteocyte ORP150 expression and cell death in vitro

Monica Montesi, Katharina Jähn, Lynda Bonewald, Susanna Stea, Barbara Bordini, Alina Beraudi

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Skeletal unloading leads to hypoxia in the bone microenvironment, resulting in imbalanced bone remodeling that favors bone resorption. Osteocytes, the mechanosensors of bone, have been demonstrated to orchestrate bone homeostasis. Hypoxic osteocytes either undergo apoptosis or actively stimulate osteoclasts to remove bone matrix during hypoxia. Oxygen regulated protein 150 (ORP150) is an endoplasmic reticulum associated chaperone that has been observed to serve an important role in the cellular adaptation to hypoxia and in preventing cellular apoptosis in various tissue types. The current study hypotheses that expression of ORP150 would be increased in osteocytes under hypoxic conditions (1% O2). The MLO Y4 osteocyte cell line was cultured under normoxic or hypoxic conditions for up to 72 h. It was demonstrated that 1% O2 significantly induced hypoxia after 16 h and up to 72 h, significantly reduced cell number at 8 and 48 h, induced cell death at 8, 24 and 48 h and induced apoptosis at 16, 24 and 48 h. Significant differences in ORP150 mRNA were observed at 72 h, however no differences were observed in the protein expression levels. The relative increase in ORP150 mRNA observed in hypoxia, compared with normoxia, may support its cytoprotective role in oxygen deprived conditions.

Original languageEnglish (US)
Pages (from-to)4248-4254
Number of pages7
JournalMolecular Medicine Reports
Volume14
Issue number5
DOIs
StatePublished - Nov 2016

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Keywords

  • Apoptosis
  • Hypoxia
  • ORP150
  • Osteocytes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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