CIZ regulates anabolic action of PTH on bone

CIZ 调节 PTH 对骨的合成代谢作用

• 批准号: 22591680
• 负责人: NAKAMOTO Tetsuya
• 金额: $ 2.91万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591680/
• 关键词: 骨・軟骨代謝学; 骨粗鬆症; CIZ; PTH; BMP; 副甲状腺ホルモン; 骨形成; PPR

We analyzed the involvement of CIZ, a BMP-inhibitory factor, in PTH-signaling. The caPPR mice express constitutively active PTH/PTHrP receptor (caPPR) in osteoblasts and in odontoblasts, and exhibit increased bone volume. The CIZKO mice also show increased bone volume. We crossed caPPR mice with CIZKO and caPPR-CIZKO mice exhibited further increased bone volume in our preliminary experiments.We had difficulties in expanding the number of caPPR-CIZKO mice, because caPPR mice are weak and because CIZKO mice have defect in spermatogenesis as reported. However, we finally got 6-10 mice in each group of 4 genotypes x 2 sex.In cell culture system, we used MC-3T3E1 cells, a osteoblast-like cell line. In order to analyze the transcriptional activity of CRE (cAMP response element), we transfected cellswith pCre-Luc vector and performed luciferase assays. When CIZ was overexpressed, caPPR-induced increase of CRE-activity did not show changes. CIZ inhibits BMP signal and PTH are reported to enhance BMP signals. Therefore we speculate that CIZ does not directly inhibit PTH-induced bone increase but that CIZ affects PTH-induced bone increase by way of inhibiting BMP signaling.

我们分析了CIZ，BMP抑制因子，在PTH信号转导的参与。caPPR小鼠在成骨细胞和成牙本质细胞中表达组成型活性PTH/PTHrP受体（caPPR），并表现出骨体积增加。CIZKO小鼠还显示出增加的骨体积。我们将caPPR小鼠与CIZKO小鼠杂交，在我们的初步实验中，caPPR-CIZKO小鼠表现出进一步增加的骨体积。我们难以扩大caPPR-CIZKO小鼠的数量，因为caPPR小鼠很弱，并且因为CIZKO小鼠有精子发生缺陷。在细胞培养体系中，我们使用了成骨样细胞系MC-3 T3 E1细胞。为了分析cAMP应答元件（CRE）的转录活性，我们用pCre-Luc载体转染细胞并进行荧光素酶分析。当CIZ过表达时，caPPR诱导的CRE活性增加没有显示出变化。CIZ抑制BMP信号，据报道PTH增强BMP信号。因此，我们推测CIZ不直接抑制PTH诱导的骨增加，但CIZ通过抑制BMP信号传导影响PTH诱导的骨增加。

项目成果

Osteopontin deficiency enhances parathyroid hormone/ parathyroid hormone related peptide receptor (PPR) signaling-induced alteration in tooth formation and odontoblastic morphology.

• DOI: 10.1016/j.tice.2011.02.003
• 发表时间: 2011-06
• 期刊: TISSUE & CELL
• 影响因子: 2.6
• 作者: Morishita, Maki;Ono, Noriaki;Miyai, Kentano;Nakagawa, Tomomi;Hanyu, Ryo;Nagao, Masashi;Kamolratanakul, Paksinee;Notomi, Takuya;Rittling, Susan R.;Denhardt, David T.;Kronenberg, Henry M.;Ezura, Yoichi;Hayata, Tadayoshi;Nakamoto, Tetsuya;Noda, Masaki
• 通讯作者: Noda, Masaki

Molecular mechanism of CIZ actions to exacerbate inflammation in serum-induced arthritis based on formation of positive feedback loop with IL-1 beta

基于与IL-1β形成正反馈环的CIZ作用加剧血清诱导性关节炎炎症的分子机制

• 发表时间: 2011
• 作者: Nakamoto T;Motoyoshi T;Kawasaki M;Sakuma T;Hayata T;Ezura Y;M. Noda M
• 通讯作者: M. Noda M

Kronenberg、 野田政樹PTHの骨形成促進作用はシャトリン グタンパク質CIZによって抑制される

Kronenberg, Masaki Noda PTH 的成骨促进作用受到穿梭蛋白 CIZ 的抑制。

• 发表时间: 2012
• 作者: 中元哲也;平林恭子;AlexanderValentinitsch;川崎真希理;佐久間朋美;早田匡芳;江面陽一;ErnestinaSchipani;Henry M
• 通讯作者: Henry M

Role of CIZ in Melanoma Activity for Metastasis

CIZ 在黑色素瘤转移活性中的作用

• 发表时间: 2011
• 作者: Sakuma T;Hemmi H;Notomi T;Nakamoto T;Hayata T;Ezura Y;Noda M
• 通讯作者: Noda M

CIZとIL-1βは相互に発現を誘導し、関節炎に関与する

CIZ 和 IL-1β 相互诱导表达并参与关节炎

• 发表时间: 2011
• 作者: 中元哲也;元吉貴之;川崎真希理;佐久間朋美;早田匡芳;江面陽一;野田政樹
• 通讯作者: 野田政樹