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

RANKL和OPG在脂多糖诱导骨吸收中的作用尚不清楚。因此，在第一项研究中，我们研究了反复注射LPS增加骨吸收，额外注射PBS减少骨吸收时表达RANKL-和opg的细胞数量的变化。随着骨吸收的增强，表达rankl的炎症细胞数量增加，表达opg的非炎症细胞数量减少。另一方面，随着骨吸收的减少，表达opg的炎症细胞数量增加。在炎症细胞实验中，在骨吸收增加的小鼠病变中检测到表达rankl的T细胞，在骨吸收减少的小鼠病变中检测到表达opg的多形核白细胞（PMN）。这些结果表明，T细胞和PMNs在炎症性骨吸收的调节中起重要作用。第二项研究的目的是检查B细胞是否真的影响体内炎症性骨吸收。在小鼠牙龈内反复注射脂多糖，比较正常小鼠、缺乏B细胞和T细胞的SCID小鼠和B细胞重建SCID小鼠的牙槽骨吸收情况。此外，我们还研究了脂多糖刺激下的B细胞是否参与体外破骨细胞的形成。结果表明，B细胞重构SCID小鼠组炎症性骨吸收明显强于SCID小鼠组。此外，在体外实验中，脂多糖刺激的B细胞增强了破骨细胞的生成，抗tnf -α抗体完全阻断了脂多糖刺激的B细胞诱导的破骨细胞生成。提示B细胞通过TNF-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.