骨桥蛋白作为关节炎破骨细胞生成的正向调节因子。

Osteopontin as a positive regulator in the osteoclastogenesis of arthritis.

作者信息

Ishii Taeko, Ohshima Shiro, Ishida Tetsushi, Mima Toru, Tabunoki Youichiro, Kobayashi Hideyuki, Maeda Masahiro, Uede Toshimitsu, Liaw Lucy, Kinoshita Naokazu, Kawase Ichiro, Saeki Yukihiko

机构信息

Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.

出版信息

Biochem Biophys Res Commun. 2004 Apr 9;316(3):809-15. doi: 10.1016/j.bbrc.2004.02.124.

DOI:10.1016/j.bbrc.2004.02.124

PMID:15033472

Abstract

We examined the role of osteopontin (OPN) in the osteoclastogenesis of arthritis using collagen-induced arthritis (CIA). Cells from arthritic joints of wild-type (OPN +/+) mice spontaneously developed bone-resorbing osteoclast-like cells (OCLs). The cultured cells showed an enhanced expression of receptor activator of nuclear factor kappaB ligand (RANKL) and a decreased expression of osteoprotegerin (OPG). The addition of OPG reduced the number of OCLs, indicating that the osteoclastogenesis depends on the RANK/RANKL/OPG system. The cells also produced OPN abundantly and anti-OPN neutralizing antibodies suppressed the development of OCLs. Moreover, the addition of OPN increased the expression of RANKL and augmented differentiation of OCLs from OPN-deficient (OPN -/-) cells. OPN, like the combination of 1alpha,25-dihydroxyvitamin D(3) and dexamethasone, also enhanced the RANKL expression and decreased OPG expression in a stromal cell line, ST2. These results suggest that OPN acts as a positive regulator in the osteoclastogenesis of arthritis through the RANK/RANKL/OPG system.

摘要

我们利用胶原诱导的关节炎（CIA）研究了骨桥蛋白（OPN）在关节炎破骨细胞生成中的作用。野生型（OPN +/+）小鼠关节炎关节的细胞自发形成了具有骨吸收功能的破骨细胞样细胞（OCLs）。培养的细胞显示核因子κB受体激活剂配体（RANKL）表达增强，骨保护素（OPG）表达降低。添加OPG可减少OCLs的数量，表明破骨细胞生成依赖于RANK/RANKL/OPG系统。这些细胞还大量产生OPN，抗OPN中和抗体可抑制OCLs的形成。此外，添加OPN可增加RANKL的表达，并增强OPN缺陷（OPN -/-）细胞向OCLs的分化。与1α,25 - 二羟维生素D(3)和地塞米松联合使用时一样，OPN也增强了基质细胞系ST2中RANKL的表达并降低了OPG的表达。这些结果表明，OPN通过RANK/RANKL/OPG系统在关节炎破骨细胞生成中起正向调节作用。