Possible involvement of elastase in enhanced osteoclast differentiation by neutrophils through degradation of osteoprotegerin.
Possible involvement of elastase in enhanced osteoclast differentiation by neutrophils through degradation of osteoprotegerin.
复制标题
弹性蛋白酶可能通过降解骨保护素参与中性粒细胞增强破骨细胞的分化。
DOI：
10.1016/j.bone.2019.115216
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发表时间：
2020
期刊：
影响因子：
4.1
通讯作者：
Kamijo R
中科院分区：
文献类型：
--
作者：
Sugisaki R;Miyamoto Y;Yoshimura K;Sasa K;Kaneko K;Tanaka M;Itose M;Inoue S;Baba K;Shirota T;Chikazu D;Kamijo R
中性粒细胞是牙周炎、类风湿性关节炎等炎症性疾病病变部位最丰富的白细胞之一。这些疾病伴随着骨丢失，这影响了患者的生活质量。然而，中性粒细胞在炎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，人类中性粒细胞增强破骨细胞分化的小鼠骨髓细胞与小鼠成骨细胞在活性维生素D3的存在下共培养。中性粒细胞弹性蛋白酶的合成抑制剂elastatinal可显著抑制破骨细胞的分化。此外，我们发现人中性粒细胞降解人重组骨保护素（OPG），一种核因子κB（RANK）配体（RANKL）的诱饵受体，一种由成骨细胞表达的破骨细胞分化诱导因子。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）可抑制中性粒细胞对OPG的降解。重组人中性粒细胞弹性蛋白酶在其死亡结构域样区域降解人OPG。这些结果表明，弹性蛋白酶降解OPG至少部分地促进了中性粒细胞对破骨细胞的分化。中性粒细胞可能在炎性骨丢失中起重要作用。
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.