title: Histone demethylase Jmjd3 regulates osteoblast apoptosis through targeting anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bim.
abstract: 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.
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang 110002, PR China; Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Tokushima 770-8504, Japan. Electronic address: missyangdi@hotmail.com.
authors.forename: Di
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Teramachi
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Tokushima 770-8504, Japan. Electronic address: tat-hane@tokushima-u.ac.jp.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Haneji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; C089212:protein kinase D; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Bcl-2; Bim; Histone demethylation; Jmjd3; Osteoblast apoptosis; Protein kinase D1