Calcif Tissue Int. 2014 Jun;94(6):640-7. doi: 10.1007/s00223-014-9847-6.
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.
众所周知，糖皮质激素（GC）诱导的骨丢失主要是由于成骨细胞功能低下和凋亡引起的。然而，GC 对成骨细胞凋亡影响的确切分子事件尚不完全清楚。最近的研究表明，E4BP4 在调节成骨细胞凋亡和分化中起重要作用。此外，E4BP4 是许多细胞中 GC 诱导凋亡所必需的 GC 调节基因。因此，我们假设 E4BP4 可能参与 GC 诱导的成骨细胞凋亡过程。采用 Western blot、逆转录-PCR、流式细胞术和 Hoechst 33258 染色来研究 E4BP4 在地塞米松（DEX）诱导的成骨细胞凋亡中的作用。结果发现，DEX 处理的成骨细胞中 E4BP4 的表达显著上调。此外，E4BP4 的耗竭显著降低了 DEX 诱导的成骨细胞凋亡。此外，E4BP4 通过促进 Bim 的诱导在 GC 诱导的成骨细胞凋亡中发挥关键作用。基于以上结果，我们可以得出结论，E4BP4 可能参与 DEX 诱导的成骨细胞凋亡过程。
