Study for the modulation of bone metabolism by a neuropeptide, substance P.

研究神经肽 P 物质调节骨代谢。

• 批准号: 11470379
• 负责人: GOTO Tetsuya
• 金额: $ 7.55万
• 依托单位: Kyushu Dental College (2001)Kyushu University (1999-2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470379/
• 关键词: Subgtance P; neurokinin- 1 receptor; osteoclast; osteoblast; bone formation; bone resorption; tachykinin; RT-PCR; サブスタンスP; ニューロキニン1レセプター; 免疫染色; 骨代謝

We studied the effects of neuropeptide, substance P (SP) on the bone metabolism. By the immunocytochemical studies indicated that SP-immunoreactive nerve fibers were located close to the bone surface, and that the SP receptors, neurokinin- 1 receptors (NK_1-Rs), were exhibited on the surfaces of osteoblasts, osteoclasts, and osteocytes.The repetition of the addition of SP induced the increase of osteoclastic bone resorption, but single addition of SP caused no effects. The increased bone resorption by SP was inhibited by the co-incubation with SP-antagonist or NK_1-R antagonist. Furthermore, the differentiation from blood monocytes to osteoclasts was stimulated by the addition of SP.Regarding with osteoblasts, mRNA of NK_1-R was expressed in 14-day cultured osteoblasts, but not in 4-day cultured osteoblasts nor rat osteoblastic cell ; Ros. Fluorescence labeled SP was bind with the osteoblasts at the bone-formation stage. The addition of SP and neurokinin B induced the increase of bone formation.These results indicated that SP stimulates the differentiation and bone resorption activity of osteoclasts through the NK_1-R, and that SP stimulated the bone formation of osteoblast at the late stage of bone formation after expression of NK_1-R on osteoblasts.

本文研究了神经肽P物质（SP）对骨代谢的影响。免疫细胞化学研究表明，SP免疫反应阳性神经纤维位于骨表面附近，SP受体神经激肽1受体（NK_1-Rs）分布于成骨细胞、破骨细胞和骨细胞表面，反复加入SP可引起骨吸收增加，而单独加入SP对骨吸收无影响。与SP拮抗剂或NK_1-R拮抗剂共同孵育可抑制SP引起的骨吸收增加。在成骨细胞中，14天培养的成骨细胞中有NK_1-R的mRNA表达，4天培养的成骨细胞和大鼠成骨细胞中均无NK_1-R的mRNA表达;荧光标记的SP在成骨期与成骨细胞结合。SP和神经激肽B均能促进成骨细胞的骨形成，提示SP通过NK_1-R促进破骨细胞的分化和骨吸收活性，SP在成骨细胞表达NK_1-R后，在骨形成后期促进成骨细胞的骨形成。

项目成果

Goto T, Kido MA, Yamaza T, Tanaka T: "Substance P and substance P receptors in bone and gingival tissue"Medical Electron Microscopy. 34. 77-85 (2001)

Goto T、Kido MA、Yamaza T、Tanaka T：“骨和牙龈组织中的 P 物质和 P 物质受体”医学电子显微镜。

Kido MA, Yamaza T, Goto T, Tanaka T: "Immunocytochemical localization of substance P neurokinin-1 receptors in rat gingival tissue"Cell and Tissue Research. 297. 213-222 (1999)

Kido MA、Yamaza T、Goto T、Tanaka T：“大鼠牙龈组织中 P 物质神经激肽-1 受体的免疫细胞化学定位”细胞和组织研究。

Goto T, Yamaza T, Kido MA, Tanaka T: "Light and electron microscopic study of the distribution of axons containing substance P and the localization of neurokinin-1 receptor in bone"Cell and Tissue Research. 293. 87-93 (1988)

Goto T、Yamaza T、Kido MA、Tanaka T：“含有 P 物质的轴突分布和骨中神经激肽 1 受体定位的光和电子显微镜研究”细胞和组织研究。

Goto T, Tanaka T: "Tachykinins and tachykinin receptors in bone"Microscopy and Research Technique. (in press).

Goto T、Tanaka T：“骨中的速激肽和速激肽受体”显微镜和研究技术。

Goto T,Yanmaza T,Kido MA,Tanaka T: "Substance P activates osteoclast formation and osteoclastic bone resorption through the neurokinin-1 receptor."Acta Histochemica et Cytochemica. (in press). (2001)

Goto T、Yanmaza T、Kido MA、Tanaka T：“P 物质通过神经激肽-1 受体激活破骨细胞形成和破骨细胞骨吸收。”组织化学与细胞化学学报。