期刊
JOURNAL OF BONE AND MINERAL METABOLISM
卷 30, 期 4, 页码 474-484出版社
SPRINGER JAPAN KK
DOI: 10.1007/s00774-011-0346-9
关键词
Homocysteine; Endoplasmic reticulum stress; Osteoblast; Osteoporosis
资金
- Ministry of Health & Welfare, Republic of Korea [A040018]
- Ministry for Health, Welfare and Family Affairs [A092258, A084948]
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [314-2008-1-E00113]
- Korea Health Promotion Institute [A040018] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [314-2008-1-E00113] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Hyperhomocysteinemia has been shown to increase the incidence of osteoporosis and osteoporotic fractures. Endoplasmic reticulum (ER) stress was recently shown to be associated with apoptosis in several types of cells. In this study, we determined the effect of homocysteine (Hcy) on the apoptosis of osteoblastic cells and investigated whether ER stress participates in Hcy-induced osteoblast apoptosis. Human osteoblastic cells were incubated with Hcy. Hcy dose-dependently decreased cell viability and increased apoptosis in osteoblastic cells. Osteoblastic cells are more susceptible to Hcy-mediated cell death than other cell types. Expression of cleaved caspase-3 was significantly increased by Hcy, and pretreatment with caspase-3 inhibitor rescued the cell viability by Hcy. Hcy treatment led to an increase in release of mitochondrial cytochrome c. It also triggered ER stress by increased expression of glucose-regulated protein 78, inositol-requiring transmembrane kinase and endonuclease 1 alpha (IRE-1 alpha), spliced X-box binding protein, activating transcription factor 4, and C/EBP homologous protein. Silencing IRE-1 alpha expression by small interfering RNA effectively suppressed Hcy-induced apoptosis of osteoblastic cells. Our results suggest that hyperhomocysteinemia induces apoptotic cell death in osteoblasts via ER stress.
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