The Affiliated Tai'an City Central Hospital of Qingdao University, Tai'an, 271000 Shandong Province, China.
Department of Stomatology, Xuzhou Central Hospital, Xuzhou, 221000 Jiangsu Province, China.
Oxid Med Cell Longev. 2023 Jan 12;2023:2975193. doi: 10.1155/2023/2975193. eCollection 2023.
Excessive bone resorption due to increased inflammatory factors is a common feature of inflammatory lytic bone diseases. This group of diseases is effectively treated with drugs. In recent years, many studies have reported that traditional Chinese medicine herbs have substantial effects on inflammation, osteoclast differentiation and maturation, and bone destruction. Herein, we investigated the effects of osthole (OST) on lipopolysaccharide- (LPS-) induced macrophage polarization, inflammatory responses, and osteolysis. In vitro, we used immunofluorescence and quantitative real-time polymerase chain reaction assays to confirm whether bone marrow-derived macrophages showed an increased expression of inflammatory factors, such as interleukin-6, iNOS, CCR7, and CD86, in the presence of LPS. However, we found that such expression was suppressed and that the M2 macrophage expression increased in the presence of OST. OST reduced LPS- and RANKL-induced intracellular reactive oxygen species production in the bone marrow-derived macrophages. Further, it potently suppressed osteoclast differentiation and osteoclast-specific gene expression by suppressing the P38/MAPK and NF-B pathways. Consistent with the in vitro observations, OST greatly ameliorated LPS-induced bone resorption and modulated the ratio of macrophages at the site of osteolysis. Taken together, OST has great potential for use in the management of osteolytic diseases.
由于炎症因子增加导致的过度骨吸收是炎症性溶骨性骨病的共同特征。这组疾病可以通过药物有效治疗。近年来，许多研究报告称，中药对炎症、破骨细胞分化和成熟以及骨质破坏有显著效果。在此，我们研究了蛇床子素（OST）对脂多糖（LPS）诱导的巨噬细胞极化、炎症反应和溶骨性的影响。在体外，我们使用免疫荧光和实时定量聚合酶链反应检测来确认骨髓来源的巨噬细胞在 LPS 存在下是否会增加炎症因子（如白细胞介素 6、诱导型一氧化氮合酶、CCR7 和 CD86）的表达。然而，我们发现这种表达被抑制，并且在 OST 存在下 M2 巨噬细胞表达增加。OST 减少了 LPS 和 RANKL 诱导的骨髓来源巨噬细胞内活性氧的产生。此外，它通过抑制 P38/MAPK 和 NF-B 通路强烈抑制破骨细胞分化和破骨细胞特异性基因表达。与体外观察一致，OST 极大地改善了 LPS 诱导的骨质吸收，并调节了溶骨性部位巨噬细胞的比例。总之，OST 在管理溶骨性疾病方面具有巨大潜力。
