Mechanism for the secretion of phosphaturic hormone FGF23 to blood

磷酸盐激素FGF23向血液分泌的机制

• 批准号: 21791028
• 负责人: YAMAZAKI Miwa
• 金额: $ 2.83万
• 依托单位: Research Institute, Osaka Medical Center for Maternal and Child Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791028/
• 关键词: FGF23; 骨吸収; 血中分泌; 破骨細胞

FGF23 is a phosphaturic hormone which is produced by bone and exerts its effects in kidney by increasing the urinary phosphate excretion. Although FGF23 is considered as a hormone, the mechanism for the regulation of its blood levels remains unclear. It is reported that treatment with a bisphosphonate, an inhibitor of bone resorption, is associated with increased levels of FGF23 in patients with osteogenesis imperfecta. Therefore, in the current study, we have tested the hypothesis by animal experiments that FGF23 produced by osteocytes is stored in bone matrix, and released to circulation in association with osteoclastic bone resorption. Administration of factors which stimulate bone resorption to mice resulted in the increased levels of serum FGF23, suggesting that osteoclastic bone resorption is involved in the secretion of FGF23 to blood.

FGF23是一种由骨骼产生，通过增加尿磷排泄在肾脏发挥作用的磷酸激素。尽管FGF23被认为是一种激素，但其调节血液水平的机制仍不清楚。据报道，骨吸收抑制剂双膦酸类药物的治疗与成骨不全患者体内FGF23水平升高有关。因此，在本研究中，我们通过动物实验验证了这一假说，即骨细胞产生的FGF23储存在骨基质中，并与破骨细胞性骨吸收相关地释放到循环中。给予小鼠刺激骨吸收的因子后，血清FGF23水平升高，提示破骨细胞性骨吸收参与了FGF23向血液的分泌。

项目成果

Signaling of extracellular inorganic phosphate up-regulates cyclin D1 expression in proliferating chondrocytes via the Na+/Pi cotransporter Pit-1 and Raf/MEK/ERK pathway

• DOI: 10.1016/j.bone.2010.08.006
• 发表时间: 2010-11-01
• 期刊: BONE
• 影响因子: 4.1
• 作者: Kimata, Masaaki;Michigami, Toshimi;Ozono, Keiichi
• 通讯作者: Ozono, Keiichi

Signal transduction triggered by extracellular inorganic phospbate involves FGF reoeptor and influences the FGF23 signaling

细胞外无机磷酸盐触发的信号转导涉及 FGF 受体并影响 FGF23 信号传导

• 发表时间: 2010
• 作者: Yamazaki M;Ozono K;Okada T;Ohata Y;Tachikawa K;Kondou H;Michigami T.;山崎美和
• 通讯作者: 山崎美和

Both FGF23 and extracellular phosphate activate Raf/MEK/ERK pathway via FGF receptors in HEK293 cells.

FGF23 和细胞外磷酸盐均通过 HEK293 细胞中的 FGF 受体激活 Raf/MEK/ERK 通路。

• 发表时间: 2010
• 期刊: J Cell Biochem 111
• 作者: Yamazaki M;Ozono K;Okada T;Tachikawa K;Kondou H;Ohata Y;Michigami T.
• 通讯作者: Michigami T.

Signal transduction triggered by extracellular inorganic phosphate involves FGF receptor and influences the FGF23 signaling.

细胞外无机磷酸盐触发的信号转导涉及 FGF 受体并影响 FGF23 信号传导。

• 发表时间: 2010
• 作者: Yamazaki M;Ozono K;Okada T;Ohata Y;Tachikawa K;Kondou H;Michigami T.
• 通讯作者: Michigami T.