TY - JOUR
T1 - Histone demethylase Jmjd3 regulates osteoblast apoptosis through targeting anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bim
AU - Yang, Di
AU - Okamura, Hirohiko
AU - Teramachi, Jumpei
AU - Haneji, Tatsuji
N1 - Funding Information:
We would like to thank Dr. Omar M. M. Rodis for his help in the preparation of this manuscript. We also thank the Support Center for Advanced Medical Sciences, Institute of Biomedical Sciences, Tokushima University Graduate School, for technical support. This study was supported by the Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan ( 21592330 and 23592703 ), the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care , Takeda Science Foundation ( 10KI171 ), and the National Natural Science Foundation of China ( 81500843 ). The authors declare no potential conflicts of interest with this article.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Posttranslational modifications including histone methylation regulate gene transcription through directly affecting the structure of chromatin. Trimethylation of histone H3K27 (H3K27me3) contributes to gene silencing and the histone demethylase Jumonji domain-containing 3 (Jmjd3) specifically removes the methylation of H3K27me3, followed by the activation of gene expression. In the present study, we explored the roles of Jmjd3 in regulating osteoblast apoptosis. Knockdown of Jmjd3 promoted osteoblast apoptosis induced by serum deprivation with decreased mitochondrial membrane potential and increased levels of caspase-3 activation, PARP cleavage, and DNA fragmentation. B cell lymphoma-2 (Bcl-2), an anti-apoptotic protein, was down-regulated by knockdown of Jmjd3 through retaining H3K27me3 on its promoter region. Knockdown of Jmjd3 increased the pro-apoptotic activity of Bim through inhibiting ERK-dependent phosphorylation of Bim. Protein kinase D1 (PKD1), which stimulates ERK phosphorylation, decreased in the Jmjd3-knockdown cells and introduction of PKD1 relieved osteoblast apoptosis in the Jmjd3-knockdown cells through increasing ERK-regulated Bim phosphorylation. These results suggest that Jmjd3 regulates osteoblast apoptosis through targeting Bcl-2 expression and Bim phosphorylation.
AB - Posttranslational modifications including histone methylation regulate gene transcription through directly affecting the structure of chromatin. Trimethylation of histone H3K27 (H3K27me3) contributes to gene silencing and the histone demethylase Jumonji domain-containing 3 (Jmjd3) specifically removes the methylation of H3K27me3, followed by the activation of gene expression. In the present study, we explored the roles of Jmjd3 in regulating osteoblast apoptosis. Knockdown of Jmjd3 promoted osteoblast apoptosis induced by serum deprivation with decreased mitochondrial membrane potential and increased levels of caspase-3 activation, PARP cleavage, and DNA fragmentation. B cell lymphoma-2 (Bcl-2), an anti-apoptotic protein, was down-regulated by knockdown of Jmjd3 through retaining H3K27me3 on its promoter region. Knockdown of Jmjd3 increased the pro-apoptotic activity of Bim through inhibiting ERK-dependent phosphorylation of Bim. Protein kinase D1 (PKD1), which stimulates ERK phosphorylation, decreased in the Jmjd3-knockdown cells and introduction of PKD1 relieved osteoblast apoptosis in the Jmjd3-knockdown cells through increasing ERK-regulated Bim phosphorylation. These results suggest that Jmjd3 regulates osteoblast apoptosis through targeting Bcl-2 expression and Bim phosphorylation.
KW - Bcl-2
KW - Bim
KW - Histone demethylation
KW - Jmjd3
KW - Osteoblast apoptosis
KW - Protein kinase D1
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U2 - 10.1016/j.bbamcr.2016.01.006
DO - 10.1016/j.bbamcr.2016.01.006
M3 - Article
C2 - 26795455
AN - SCOPUS:84956688215
VL - 1863
SP - 650
EP - 659
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 4
ER -