Mechanisms of osteoclastic bone resorption on an extracellular product from periodontal pathogenic microorganisms

牙周病原微生物细胞外产物破骨细胞骨吸收机制

• 批准号: 08672205
• 负责人: KURIHARA Noriyoshi
• 金额: $ 1.47万
• 依托单位: MEIKAI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672205/
• 关键词: osteoclast; tyrosinekinase; bone resorption; extracellular prpduct from periodontal pathogenic microorganism; 歯周病原性細菌 内毒素; 歯周病原性細菌

STK is a member of the hepatocyte growth factor (HGF) receptor family. The ligand for STK,macrophage stimulating protein (MSP) is a serum protein activated by members of the coagulation cascade. The RON gene was the murine homologue of the murine STK.In this report, we examined the role of MSP-RON in the signal pathway of human osteoclasts. Using anti-RON antibody, we detected RON expressed in multinucleated osteoclast-like cells (OCL) formed in the culture of human bone marrow cells. To determine the bone resorption, we placed OCL on ceramic calcium phosphate thin films formed on quartz supports coated slide (Millenium Biologix) and measured resorption. MSP stimulated the pit formation by OCL in a dose-dependent manner. MSP (50 ng/m1) cause a fourfold increase in pit area compared to control.Furthermore, we examined the effects of MSP and HGF on OCL formation from purified populations of hematopoietic progenitors. OCL expressing the osteoclast phenotype were identified by their cross-reactivity with the 23c6 monoclonal antibody. HGF (50 ng/ml) stimulated the differentiation of progenitors to 23c6-positive OCL,but did not enhance the bone absorption. In contrast, MSP did not affect the proliferation of osteoclast precursors but stimulated bone resorption by OCL.We conclude that MSP signal transduction pathway plays a distinct role in the bone absorption compared with HGF.

STK是肝细胞生长因子（HGF）受体家族的成员。巨噬细胞刺激蛋白（MSP）是STK的配体，是一种由凝血级联成员激活的血清蛋白。RON基因是小鼠stk的小鼠同源基因。在本报告中，我们研究了MSP-RON在人类破骨细胞信号通路中的作用。我们利用抗RON抗体检测了RON在人骨髓细胞培养形成的多核破骨细胞样细胞（OCL）中的表达。为了确定骨吸收，我们将OCL放置在石英支架涂层载玻片（Millenium Biologix）上形成的陶瓷磷酸钙薄膜上，并测量骨吸收。MSP以剂量依赖的方式刺激OCL形成坑。与对照相比，MSP （50 ng/m1）使坑面积增加了四倍。此外，我们还研究了MSP和HGF对纯化的造血祖细胞群体OCL形成的影响。通过与23c6单克隆抗体的交叉反应性鉴定表达破骨细胞表型的OCL。HGF （50 ng/ml）刺激祖细胞向23c6阳性OCL分化，但对骨吸收无促进作用。相反，MSP不影响破骨细胞前体的增殖，但刺激OCL的骨吸收。我们认为，与HGF相比，MSP信号转导通路在骨吸收中起着不同的作用。

项目成果

Shimoyama M., Tatsumi J and Kurihara N.: "Efect of Lipopolysaccharide, an extracellular products from periodontal pathogenic microorganisms, on osteoclast formation (Japanese)" Jpn.J.Periodont. 39(39). 313-323 (1996)

Shimoyama M.、Tatsumi J 和 Kurihara N.：“脂多糖（牙周病原微生物的细胞外产物）对破骨细胞形成的影响（日语）”Jpn.J.Periodont。

Kurihara N., Iwama A., Tatsumi J., Ikeda K.Suda T.: "Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclat-like cells" Blood. 87・9. 3704-3710 (1996)

Kurihara N.、Iwama A.、Tatsumi J.、Ikeda K.Suda T.：“巨噬细胞刺激蛋白激活破骨细胞上的 STK 受体酪氨酸激酶，并促进破骨细胞样细胞的骨吸收”血液 87・9。 (1996)

栗原 徳善, 辰巳 順一, 池田 克已, 岩間 厚志, 須田 年生: "新規受容体型チロシンキナーゼ;STKは、破骨細胞に発現し、その結合因子MSPは、骨吸収を促進する" 日骨代謝誌. 14・1. 6-13 (1996)

Tokuyoshi Kurihara、Junichi Tatsumi、Katsumi Ikeda、Atsushi Iwama 和 Toshiyuki Suda：“一种新型受体酪氨酸激酶；STK 在破骨细胞中表达，其结合因子 MSP 促进骨吸收”日本骨代谢杂志 14・1.6-13（ 1996）

Kurihara N., Iwama A., Tatsumi J., Ikeda K.and Suda T.: "Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclat-like cells" Blood. 87(9). 3704-3710 (1996)

Kurihara N.、Iwama A.、Tatsumi J.、Ikeda K. 和 Suda T.：“巨噬细胞刺激蛋白激活破骨细胞上的 STK 受体酪氨酸激酶，并促进破骨细胞样细胞的骨吸收”血液。

栗原徳善: "Macrophage-Stimulating Protain Activates STK Receptor Tyrosine Kinase on Osteoclast and Facilitates Bone Resorption by Osteoclast-like Cells." Blood. 87・9. 3704-3710 (1996)

Tokuyoshi Kurihara：“巨噬细胞刺激蛋白激活破骨细胞上的 STK 受体酪氨酸激酶并促进破骨细胞样血液的骨吸收。”87・9。