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Medical Molecular Morphology
Published in: Medical Molecular Morphology 3/2019

01-09-2019 | Glucocorticoid | Original Paper

Heme oxygenase-1 prevents glucocorticoid and hypoxia-induced apoptosis and necrosis of osteocyte-like cells

Authors: Hiroki Yamamoto, Masazumi Saito, Tsuyoshi Goto, Keiichiro Ueshima, Masashi Ishida, Shigeki Hayashi, Kazuya Ikoma, Osam Mazda, Toshikazu Kubo

Published in: Medical Molecular Morphology | Issue 3/2019

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Abstract

Glucocorticoids and hypoxia is considered to promote osteocyte apoptosis and necrosis, which are observed in glucocorticoid-associated osteonecrosis and osteoporosis. Heme oxygenase-1 (HO-1) induced by hemin is reported to have cytoprotective effects in ischemic diseases. The objective of this study was to evaluate the effect of HO-1 on osteocyte death caused by glucocorticoids and hypoxia. We confirmed that hemin induced HO-1 expression in MLO-Y4 mouse osteocytes. MLO-Y4 was cultured with dexamethasone (Dex) under hypoxia (DH group). Furthermore, these cells were cultured with hemin (DH-h group) or hemin and zinc protoporphyrin IX (an HO-1 inhibitor) (DH-h-PP group). The rates of apoptosis and necrosis of these groups were analyzed by flow cytometry and compared with cells cultured under normal condition. Both apoptosis and necrosis increased in the DH group. Hemin administration significantly reduced cell death caused by glucocorticoids and hypoxia in the DH-h group, and its effect was attenuated by the HO-1 inhibitor in DH-h-PP group. Capase-3 activity significantly decreased in the DH-h group. This implied that the cell death inhibition effect due to hemin is mediated by HO-1 and caspase-3. HO-1 induction may be useful in the treatment of glucocorticoid-associated osteonecrosis and osteoporosis.
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Metadata
Title
Heme oxygenase-1 prevents glucocorticoid and hypoxia-induced apoptosis and necrosis of osteocyte-like cells
Authors
Hiroki Yamamoto
Masazumi Saito
Tsuyoshi Goto
Keiichiro Ueshima
Masashi Ishida
Shigeki Hayashi
Kazuya Ikoma
Osam Mazda
Toshikazu Kubo
Publication date
01-09-2019
Publisher
Springer Japan
Published in
Medical Molecular Morphology / Issue 3/2019
Print ISSN: 1860-1480
Electronic ISSN: 1860-1499
DOI
https://doi.org/10.1007/s00795-018-00215-0

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