A basic research on coupling factors between bone resorption and bone formation

RANKL和OPG在脂多糖诱导的骨吸收中的作用尚不清楚。因此，在第一项研究中，我们检测了重复注射脂多糖增加骨吸收，而额外注射PBS减少骨吸收时RANKL和OPG表达细胞数量的变化。随着骨吸收的增强，表达RANKL的炎性细胞增多，表达OPG的非炎性细胞减少。另一方面，表达OPG的炎症细胞数量随着骨吸收的减少而增加。在炎性细胞检测中，骨吸收增加的小鼠皮损中检测到RANKL表达的T细胞，骨吸收减少的小鼠皮损中检测到表达OPG的中性粒细胞。这些结果提示T细胞和PMN在炎症性骨吸收的调节中起着重要作用。第二项研究的目的是探讨B细胞是否真的影响体内的炎症性骨吸收。对正常小鼠、B细胞和T细胞缺失的SCID小鼠和B细胞重组的SCID小鼠牙槽骨吸收进行了组织病理学比较。此外，我们还检测了脂多糖刺激的B细胞是否参与了体外破骨细胞的形成。结果显示，B细胞重组SCID鼠组较SCID鼠组表现出更强的炎性骨吸收。此外，在体外，脂多糖刺激的B细胞促进破骨细胞的生成，抗肿瘤坏死因子-α抗体完全阻断内毒素刺激的B细胞诱导的破骨细胞生成。提示B细胞通过肿瘤坏死因子-α促进炎性骨吸收。

The involvement of RANKL and OPG in lipopolysaccharide-induced bone resorption is not well understood. So in the first study, we examined changes in the number of RANKL- and OPG-expressing cells when bone resorption was increased by repeated injections of LPS and decreased by additional injection of PBS. The number of RANKL-expressing inflammatory cells increased and OPG-expressing non-inflammatory cells decreased with enhancement of bone resorption. On the other hand, the number of OPG-expressing inflammatory cells increased with decrease of bone resorption. Of the inflammatory cells assay, RANKL-expressing T cells were detected in the lesions of mice with increased bone resorption and OPG-expressing polymorphonuclear leukocytes (PMN) were detected in the lesions of mice with decreased bone resorption. These results suggested that T cells and PMNs play important roles in the regulation of inflammatory bone resorption.The aim of the second study was to examine whether B cells truly influence inflammatory bone resorption in vivo. Alveolar bone resorption in normal mice, in SCID mice that lack both B and T cells, and in B cell-reconstituted SCID mice were compared histopathologically after repeated injections of lipopolysaccharide into mouse gingival. Furthermore, we examined whether the B cells that are stimulated by lipopolysaccharide are involved in osteoclastogenesis in vitro. As a result, the B cell-reconstituted SCID mice group showed stronger inflammatory bone resorption than the SCID mice group. Also, in vitro, lipopolysaccharide-stimulated B cells enhanced osteoclastogenesis and anti-TNF-α antibody completely blocked osteoclastogenesis induced by lipopolysaccharide-stimulated B cells. These results suggest that B cells promote inflammatory bone resorption through TNF-α.