title: Glucocorticoid induced osteoblast apoptosis by increasing E4BP4 expression via up-regulation of Bim.
abstract: It is well known that glucocorticoid (GC)-induced bone loss is caused primarily by hypofunction and apoptosis of osteoblasts. However, the precise molecular events underlying the effect of GC on osteoblast apoptosis are not fully understood. Recent studies implicated an important role of E4BP4 in the regulation of osteoblast apoptosis and differentiation. Furthermore, E4BP4 is a GC-regulated gene required for GC-induced apoptosis in many cells. Therefore, we hypothesize that E4BP4 may be implicated in the process of GC-induced osteoblast apoptosis. Western blot, reverse-transcription-PCR, flow cytometry, and Hoechst 33258 staining were employed to investigate the role of E4BP4 in dexamethasone (DEX)-induced osteoblast apoptosis. We found that the expression of E4BP4 is significantly up-regulated in osteoblasts exposed to DEX. Furthermore, the depletion of E4BP4 significantly decreased DEX-induced osteoblast apoptosis. In addition, E4BP4 plays a crucial role in GC-evoked apoptosis of osteoblasts by enabling induction of Bim. On the basis of these results above, we can draw the conclusion that E4BP4 may contribute to the process of DEX-induced osteoblast apoptosis.
authors.forename: Fangjing
authors.initials: F
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yueping
authors.initials: Y
authors.lastname: OuYang
authors.forename: Huapeng
authors.initials: H
authors.lastname: Guan
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Ni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis*; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D003907:Dexamethasone / Q000633:toxicity*; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000633:toxicity*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D005938:Glucocorticoids; D008565:Membrane Proteins; C497441:Nfil3 protein, mouse; D011518:Proto-Oncogene Proteins; D003907:Dexamethasone