Studies on the immune-response of γδT cells in animal model with osteoporosis taking bisphosphonates.

本研究的目的是在基础环境下检测唑来膦酸盐(ZOL)、强的松龙(PSL)和脂多糖(LPS)对小鼠核因子-kB受体激活物(RANKL)、护骨素(OPG)和T细胞受体(TCR)表达的影响。采用C57BL/6、NOD-SCID和NOD-SCID移植外周血单个核细胞。取外周血检测OPG和RANKL。取股骨和下颌骨进行组织形态计量学分析。用Micro-CT评价骨标本的微结构。免疫组织化学方法检测TCR的表达。组织形态计量学分析显示，ZOL可降低OS/BS和OV/BV。Ob.S/BS和Oc.S/BS降低。在同时服用ZOL和PSL的C57BL/6组，口腔黏膜内注射内毒素可增加血清RANKL水平。我们发现，联合应用ZOL和PSL降低了骨转换，而且联合使用会导致不同的TCR表达模式。提示PSL和LPS对ZOL的骨代谢和免疫应答有不同的影响。

The aim of this study was to examine, in a basic setting, changes in receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG), and the expression of T cell receptor (TCR) in mice treated with zoledronate (ZOL) and prednisolone (PSL) and lipopolysaccharide (LPS). C57BL/6, NOD-scid, and NOD-scid transplanted peripheral blood mononuclear cells (PBMC) were used. Peripheral blood samples were obtained to assay for OPG and RANKL. Femur and mandible were prepared for histomorphometric analysis. The microarchitecture of the bone samples was assessed by micro-CT. TCR expression was analyzed by immunohistochemistry. Histomorphometric analysis indicated that OS/BS and OV/BV were lowered by the administration of ZOL. Ob.S/BS and Oc.S/BS were decreased. In the C57BL/6 group taking both of ZOL and PSL, injection of LPS into the oral mucosa increased the levels of serum-RANKL. We showed that combined administration of ZOL with PSL decreased bone turn-over, and furthermore the combination causes a different pattern of TCR expression. These findings suggest that PSL and LPS have differential effects on bone metabolism and the immunoresponse to ZOL.