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CCAAT/增强子结合蛋白β（C/EBPβ）是 1,25 二羟维生素 D3（1,25D3）诱导成骨细胞核因子κB 受体激活剂配体（RANKL）表达的重要介质。

CCAAT/enhancer-binding protein beta (C/EBPβ) is an important mediator of 1,25 dihydroxyvitamin D3 (1,25D3)-induced receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblasts.

机构信息

Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Korea.

Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea.

出版信息

BMB Rep. 2019 Jun;52(6):391-396. doi: 10.5483/BMBRep.2019.52.6.166.

DOI:10.5483/BMBRep.2019.52.6.166
PMID:30355436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6605518/
Abstract

Receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoblasts is regulated by 1,25-dihydroxyvitamin D3 (1,25D3). CCAAT/enhancer-binding protein beta (C/EBPβ) has been proposed to function as a transcription factor and upregulate RANKL expression, but it is still uncertain how C/EBPβ is involved in 1,25D3-induced RANKL expression of osteoblasts. 1,25D3 stimulation increased the expression of RANKL and C/EPBβ genes in osteoblasts and enhanced phosphorylation and stability of these proteins. Moreover, induction of RANKL expression by 1,25D3 in osteoblasts was downregulated upon knockdown of C/EBPβ. In contrast, C/EBPβ overexpression directly upregulated RANKL promoter activity and exhibited a synergistic effect on 1,25D3-induced RANKL expression. In particular, 1,25D3 treatment of osteoblasts increased C/EBPβ protein binding to the RANKL promoter. In conclusion, C/EBPβ is required for induction of RANKL by 1,25D3. [BMB Reports 2019; 52(6): 391-396].

摘要

核因子 κB 受体激活剂配体 (RANKL) 在成骨细胞中的表达受 1,25-二羟维生素 D3(1,25D3)调节。CCAAT/增强子结合蛋白β (C/EBPβ) 被提议作为转录因子并上调 RANKL 表达，但 C/EBPβ 如何参与 1,25D3 诱导的成骨细胞 RANKL 表达仍不确定。1,25D3 刺激增加了成骨细胞中 RANKL 和 C/EPBβ 基因的表达，并增强了这些蛋白的磷酸化和稳定性。此外，1,25D3 在成骨细胞中诱导的 RANKL 表达在 C/EBPβ 敲低时被下调。相比之下，C/EBPβ 的过表达直接上调了 RANKL 启动子活性，并对 1,25D3 诱导的 RANKL 表达表现出协同作用。特别是，1,25D3 处理成骨细胞增加了 C/EBPβ 蛋白与 RANKL 启动子的结合。总之，C/EBPβ 是 1,25D3 诱导 RANKL 所必需的。[BMB 报告 2019; 52(6): 391-396]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/9fba46baa9b3/bmb-52-391f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/1110bc0f60ce/bmb-52-391f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/4b104d65668a/bmb-52-391f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/06c389e4b09f/bmb-52-391f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/9fba46baa9b3/bmb-52-391f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/1110bc0f60ce/bmb-52-391f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/4b104d65668a/bmb-52-391f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/06c389e4b09f/bmb-52-391f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8f/6605518/9fba46baa9b3/bmb-52-391f4.jpg

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