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

  • Hiroki Yamamoto
  • Masazumi SaitoEmail author
  • Tsuyoshi Goto
  • Keiichiro Ueshima
  • Masashi Ishida
  • Shigeki Hayashi
  • Kazuya Ikoma
  • Osam Mazda
  • Toshikazu Kubo
Original Paper


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.


Heme oxygenase-1 Hemin Osteonecrosis of the femoral head Osteoporosis Hypoxia 



JSPS KAKENHI; Grant Number: 15K20011.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2019

Authors and Affiliations

  • Hiroki Yamamoto
    • 1
  • Masazumi Saito
    • 1
    Email author
  • Tsuyoshi Goto
    • 1
  • Keiichiro Ueshima
    • 1
  • Masashi Ishida
    • 1
  • Shigeki Hayashi
    • 1
  • Kazuya Ikoma
    • 1
  • Osam Mazda
    • 2
  • Toshikazu Kubo
    • 1
  1. 1.Department of Orthopaedics, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of Immunology, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan

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