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

STK是肝细胞生长因子（HGF）受体家族的成员。STK的配体巨噬细胞刺激蛋白（MSP）是一种由凝血级联成员激活的血清蛋白。罗恩基因是小鼠STK的同源基因，在本研究中，我们检测了MSP-罗恩在人破骨细胞信号通路中的作用。用抗罗恩抗体检测人骨髓细胞培养中形成的多核破骨细胞样细胞（OCL）中罗恩的表达。为了确定骨吸收，我们将OCL放置在石英支持物涂覆的载玻片（Millenium Biologix）上形成的陶瓷磷酸钙薄膜上并测量吸收。MSP以剂量依赖的方式刺激OCL的孔形成。MSP（50 ng/m ~ 1）可使窝面积增加4倍。此外，我们还研究了MSP和HGF对纯化的造血祖细胞OCL形成的影响。表达破骨细胞表型的OCL通过其与23 c6单克隆抗体的交叉反应性来鉴定。HGF（50 ng/ml）可促进骨细胞向23 c6阳性OCL分化，但不能促进骨吸收。与此相反，MSP不影响破骨细胞前体细胞的增殖，但刺激OCL的骨吸收。我们认为，MSP的信号转导途径在骨吸收中起着不同的作用相比，HGF。

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.