Serum calcium upregulates Fgf23 expression by Dickopf-1-mediated inhibition of Wnt/beta-catenin signaling in bone

血清钙通过 Dickopf-1 介导的骨中 Wnt/β-连环蛋白信号传导抑制上调 Fgf23 表达

• 批准号: 23592696
• 负责人: TAMAMURA Yoshihiro
• 金额: $ 3.33万
• 依托单位: Mukogawa Women's University (2012-2013)Tokyo Medical and Dental University (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592696/
• 关键词: Fgf23; Wnt; カルシウム

Fgf23 is a phosphaturic factor which is secreted from osteocytes in bone. Fgf23 plays a central role for phosphate metabolism as demonstrated by elevated serum levels of Fgf23 in hypophosphatemic diseases. Post-transcriptional modification of Fgf23 is extensively studied, however mechanisms of transcriptional regulation of Fgf23 are not fully understood. In this study, we demonstrated that serum calcium regulates Fgf23 expression by Dickopf-1-mediated inhibition of Wnt/beta-catenin signaling in bone. This result will provide the possibilities of a new therapy for hypophosphatemic diseases by using anti-Dickpof-1 antibody.

FGF23是一种由骨细胞分泌的磷酸因子。FGF23在磷酸盐代谢中起中心作用，低血磷症患者血清FGF23水平升高证明了这一点。FGF23的转录后修饰已被广泛研究，但其转录调控机制尚不完全清楚。在这项研究中，我们证明了血清钙通过Dickopf-1介导的抑制Wnt/β-catenin信号在骨中的表达来调节FGF23的表达。这一结果为利用抗Dickpof-1抗体治疗低磷血症提供了新的可能性。

项目成果

Spatiotemporal disorder in the axial skeleton development of the Mesp2-null mouse : a model of spondylocostal disostosis and spondylothoracic dysostosis

Mesp2缺失小鼠中轴骨骼发育的时空紊乱：脊椎肋骨发育不全和脊椎胸椎骨发育不全模型

• 发表时间: 2013
• 期刊: Bone
• 影响因子: 4.1
• 作者: Makino Y;Takahashi Y;Tanabe R;Tamamura Y;Watanabe T;Haraikawa M;Hamagaki M;Hata K;Kanno J;Yoneda T;Saga Y;Goseki-Sone M;Kaneko K;Yamaguchi A;Iimura T
• 通讯作者: Iimura T

Bone and tooth in calcium and phosphate metabolism

骨骼和牙齿的钙磷代谢

• 发表时间: 2012
• 期刊: Clin. Calcium
• 作者: Tamamura Y;Yamaguchi A
• 通讯作者: Yamaguchi A

Increasing participation of Sclerostin in postnatal bone development revealed by three-dimensional immunofluorescence morphometry.

三维免疫荧光形态测量显示硬化蛋白越来越多地参与出生后骨骼发育。

• DOI: 10.1016/j.bone.2012.06.019
• 发表时间: 2012
• 期刊: BONE
• 影响因子: 4.1
• 作者: Watanabe T;Tamamura Y;Hoshino A;Makino Y;Nishimura R;Kamioka H;Yoneda T;Amagasa T;Yamaguchi A;Iimura T
• 通讯作者: Iimura T

CCN3 Protein Participates in Bone Regeneration as an Inhibitory Factor

• DOI: 10.1074/jbc.m113.454652
• 发表时间: 2013-07-05
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Matsushita, Yuki;Sakamoto, Kei;Yamaguchi, Akira
• 通讯作者: Yamaguchi, Akira

Comparative morphology of the osteocyte lacunocanalicular system in various vertebrates

• DOI: 10.1007/s00774-011-0268-6
• 发表时间: 2011-11-01
• 期刊: JOURNAL OF BONE AND MINERAL METABOLISM
• 影响因子: 3.3
• 作者: Cao, Lei;Moriishi, Takeshi;Yamaguchi, Akira
• 通讯作者: Yamaguchi, Akira