Periostin has a protective role in melatonin‑induced cell apoptosis by inhibiting the eIF2α‑ATF4 pathway in human osteoblasts

Meng,Xiaotong; Zhu,Yue; Tao,Lin; Zhao,Sichao; Qiu,Shui

doi:10.3892/ijmm.2017.3300

Periostin has a protective role in melatonin‑induced cell apoptosis by inhibiting the eIF2α‑ATF4 pathway in human osteoblasts

Authors:
- Xiaotong Meng
- Yue Zhu
- Lin Tao
- Sichao Zhao
- Shui Qiu
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Affiliations: Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: November 30, 2017 https://doi.org/10.3892/ijmm.2017.3300
Pages: 1003-1012

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Abstract

The present study aimed to investigate the role of periostin (POSTN) and high melatonin concentrations in the apoptosis of hFOB 1.19 human normal fetal osteoblastic cells. hFOB 1.19 human osteoblastic cells were stably cultured and treated in different concentrations of melatonin for different durations of action. Apoptosis was assessed quantitatively using flow cytometric analysis. The results of western blot analysis demonstrated that the treatment of cells with different concentrations of melatonin for different durations of action revealed a positive association between melatonin and the expression levels of glucose‑regulated protein (GRP)78, GRP94, phosphorylated (p‑) eukaryotic initiation factor 2α (eIF2α), activating transcription factor (ATF)4, CCAAT/enhanced binding protein homologous protein (CHOP), cleaved caspase‑3, p‑c‑Jun N‑terminal kinase (JNK) and POSTN. When POSTN was inhibited, the levels of p‑JNK, CHOP, p‑eIF2α, ATF4 and cleaved caspase‑3 were significantly increased, whereas other proteins associated with the endoplasmic reticulum stress (ERS) pathways, including ATF6 and X‑box binding protein 1 (XBP1), were not significantly altered. Reverse transcription‑quantitative polymerase chain reaction analysis was also performed to assess the relative mRNA levels of ATF4, ATF6 and XBP1. The results of the present study are the first, to the best of our knowledge, to demonstrate that melatonin induced apoptosis in hFOB 1.19 human osteoblastic cells by activating the ERS‑associated eIF2α‑ATF4 pathway and subsequently triggered the cascade effects of CHOP, caspase‑3 and JNK. POSTN may function as a protective factor for osteoblasts during this process by inhibiting the eIF2α‑ATF4 pathway.

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