Neutrophils are one of the most abundant leukocytes in the sites of lesion of inflammatory diseases such as periodontitis and rheumatoid arthritis. These diseases are accompanied by bone loss, which worsens the quality of life of the patients. However, the role of neutrophils in the inflammatory bone loss has not been fully investigated. In the present study, we found that human neutrophils enhanced osteoclast differentiation from mouse bone marrow cells co-cultured with mouse osteoblasts in the presence of active vitamin D3. The enhanced osteoclast differentiation was significantly suppressed by elastatinal, a synthetic inhibitor of neutrophil elastase. Also, we found that human neutrophils degraded human recombinant osteoprotegerin (OPG), a decoy receptor for nuclear factor κB (RANK) ligand (RANKL), the essential osteoclast differentiation-inducing factor, expressed by osteoblasts. Degradation of OPG by neutrophils was suppressed by human α1-protease inhibitor, the major endogenous inhibitor of neutrophil elastase. Recombinant human neutrophil elastase degraded human OPG in its death domain-like region. These results indicated that the degradation of OPG by elastase contributed at least in part to the enhanced osteoclast differentiation by neutrophils. There is a possibility that neutrophils play an important role in inflammatory bone loss.

中文翻译：

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弹性蛋白酶可能通过降解骨保护素参与中性粒细胞的破骨细胞分化

中性粒细胞是牙周炎和类风湿性关节炎等炎性疾病病变部位最丰富的白细胞之一。这些疾病伴随着骨质流失，使患者的生活质量恶化。然而，中性粒细胞在炎症性骨丢失中的作用尚未得到充分研究。在本研究中，我们发现人类中性粒细胞在活性维生素 D3 存在下增强了与小鼠成骨细胞共培养的小鼠骨髓细胞的破骨细胞分化。增强的破骨细胞分化被弹性蛋白（一种中性粒细胞弹性蛋白酶的合成抑制剂）显着抑制。此外，我们发现人类中性粒细胞降解人类重组骨保护素 (OPG)，一种核因子 κB (RANK) 配体 (RANKL) 的诱饵受体，必需的破骨细胞分化诱导因子，由成骨细胞表达。中性粒细胞对 OPG 的降解受到人 α1-蛋白酶抑制剂（中性粒细胞弹性蛋白酶的主要内源性抑制剂）的抑制。重组人中性粒细胞弹性蛋白酶在其死亡域样区域降解人 OPG。这些结果表明，弹性蛋白酶对 OPG 的降解至少部分有助于中性粒细胞对破骨细胞分化的增强。中性粒细胞有可能在炎症性骨质流失中起重要作用。这些结果表明，弹性蛋白酶对 OPG 的降解至少部分有助于中性粒细胞对破骨细胞分化的增强。中性粒细胞有可能在炎症性骨质流失中起重要作用。这些结果表明，弹性蛋白酶对 OPG 的降解至少部分有助于中性粒细胞对破骨细胞分化的增强。中性粒细胞有可能在炎症性骨质流失中起重要作用。