Prevention of osteonecrosis of the femoral head by HO-1 inducing cell stress tolerance

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K20011
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Saito Masazumi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30614101)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: heme oxygenase-1 / hemin / osteonecrosis / hypoxia / osteoporosis / femoral

Outline of Final Research Achievements

Glucocorticoids and hypoxia is considered to promote glucocorticoid-associated osteonecrosis and osteoporosis. Heme oxygenase-1 (HO-1) induced by hemin is reported to have cytoprotective effects. The aim of this study was to evaluate the effect of HO-1 on osteocyte death 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 osteocyte death were analyzed by flow cytometry and compared with cells 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 in DH-h-PP group. This implied that the cell death inhibition effect due to hemin is mediated by HO-1.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

ステロイドと低酸素によって，骨細胞のアポトーシスおよびネクローシスが誘導されることが知られており，ステロイド関連の骨粗鬆症や特発性大腿骨頭壊死症に関与している可能性がある．本研究ではすでに臨床で使用されている薬剤であるheminによって誘導されるHO-1 (heme oxigenase-1)により，ステロイドと低酸素による骨細胞死を抑制できることが明らかになった．骨組織におけるHO-1の誘導はステロイド関連の骨壊死症や骨粗鬆症の治療に応用できる可能性を示した。