Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells
Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells
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DOI：
10.1074/jbc.m600896200
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发表时间：
2006-06-23
影响因子：
4.8
通讯作者：
Inoue, Satoshi
中科院分区：
文献类型：
--
作者：
Ichikawa, Tomoe;Horie-Inoue, Kuniko;Inoue, Satoshi
维生素K-2是血液凝固所需的重要营养素。它还在骨稳态中起关键作用，是骨质疏松症的临床有效治疗剂。我们以前证明，维生素K2是成骨细胞中骨标记基因的转录调节因子，它可能通过激活类固醇和异生素受体SXR来增强骨形成。为了探讨SXR介导的维生素K2信号网络在骨稳态，我们确定了基因上调的维生素K-2和原型SXR配体，利福平，在成骨细胞中使用寡核苷酸微阵列分析和定量逆转录PCR。14个基因被两种配体上调。其中，tsukushi，matrilin-2和CD 14抗原被证明是主要的SXR靶基因。此外，维生素K2处理增强了成骨细胞MG 63中的胶原积累。功能获得和功能丧失分析表明，富含亮氨酸的小蛋白多糖，tsukushi，有助于维生素K-2介导的胶原蛋白积累的增强。我们的研究结果表明，维生素K2在骨形成中作为细胞外基质相关基因的转录调节因子，参与胶原蛋白组装的新功能。
Vitamin K-2 is a critical nutrient required for blood coagulation. It also plays a key role in bone homeostasis and is a clinically effective therapeutic agent for osteoporosis. We previously demonstrated that vitamin K2 is a transcriptional regulator of bone marker genes in osteoblastic cells and that it may potentiate bone formation by activating the steroid and xenobiotic receptor, SXR. To explore the SXR-mediated vitamin K2 signaling network in bone homeostasis, we identified genes up-regulated by both vitamin K-2 and the prototypical SXR ligand, rifampicin, in osteoblastic cells using oligonucleotide microarray analysis and quantitative reverse transcription-PCR. Fourteen genes were up-regulated by both ligands. Among these, tsukushi, matrilin-2, and CD14 antigen were shown to be primary SXR target genes. Moreover, collagen accumulation in osteoblastic MG63 cells was enhanced by vitamin K2 treatment. Gain- and loss-of-function analyses showed that the small leucine-rich proteoglycan, tsukushi, contributestovitamin K-2-mediated enhancement of collagen accumulation. Our results suggest a new function for vitamin K2 in bone formation as a transcriptional regulator of extracellular matrix-related genes, that are involved in the collagen assembly.