IKK/NF-κB and ROS signal axes are involved in Tenacissoside H mediated inhibitory effects on LPS-induced inflammatory osteolysis.
IKK/NF-κB and ROS signal axes are involved in Tenacissoside H mediated inhibitory effects on LPS-induced inflammatory osteolysis.
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DOI：
10.1111/cpr.13535
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发表时间：
2024-01
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
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作者：
牙周病和关节置换术假体松动和不稳定均与骨质溶解相关，骨质溶解主要由促炎细胞因子触发的异常骨吸收引起。破骨细胞（OCs）是这一过程中的关键参与者。然而，关于目前一线治疗的长期疗效和副作用的担忧仍然存在。仍然需要替代疗法。这项工作的目的是研究Tenacissoside H（TDH）参与RANKL介导的OC分化以及炎性骨溶解和相关过程。在体外，使用与RANKL和M-CSF一起培养的骨髓源性巨噬细胞（BMSCs）来检测TDH在OC分化和功能中的作用。采用真实的实时定量PCR检测OC中特异性基因和炎症因子的表达。Western blot检测NF-κ B、NF-κB、MAPK通路和氧化应激相关成分。最后，采用LPS介导的颅骨骨质溶解小鼠模型来探索TDH在炎性骨质溶解中的作用。结果表明，TDH在体内可抑制OC的分化和吸收功能，下调破骨细胞特异性基因以及IL-1β、IL-6和TNF-α的转录。此外，TDH抑制IKK和NF-κB信号通路并下调ROS水平。体内研究表明，TDH改善了LPS引起的骨丢失。TDH可能是破骨细胞相关炎性溶骨性疾病的新候选药物或治疗方法。Tenacissoside H（TDH）是从Marsdenia tenacissma中提取的单体，已被证明具有抗炎和抗氧化作用。然而，TDH在骨骼疾病中的作用仍不清楚。在这项研究中，发现TDH抑制IKK/NF-κB信号通路，下调c-FOS、NFATc 1、CTSK和ATP 6v 0 d2的表达，并抑制破骨细胞分化和功能。TDH可抑制脂多糖诱导的IL-1-β、IL-6和TNF-α的转录，下调ROS水平，体内研究显示TDH可显著修复脂多糖诱导的骨丢失。TDH具有抗破骨细胞活性的临床前景。
Periodontal disease and arthroplasty prosthesis loosening and destabilization are both associated with osteolysis, which is predominantly caused by abnormal bone resorption triggered by pro‐inflammatory cytokines. Osteoclasts (OCs) are critical players in the process. Concerns regarding the long‐term efficacy and side effects of current frontline therapies, however, remain. Alternative therapies are still required. The aim of this work was to investigate the involvement of Tenacissoside H (TDH) in RANKL‐mediated OC differentiation, as well as inflammatory osteolysis and associated processes. In vitro, bone marrow‐derived macrophages (BMMs) cultured with RANKL and M‐CSF were used to detect TDH in the differentiation and function of OCs. Real‐time quantitative PCR was used to measure the expression of specific genes and inflammatory factors in OCs. Western blot was used to identify NFATc1, IKK, NF‐κB, MAPK pathway, and oxidative stress‐related components. Finally, an LPS‐mediated calvarial osteolysis mouse model was employed to explore TDH's role in inflammatory osteolysis. The results showed that in vivo TDH inhibited the differentiation and resorption functions of OCs and down‐regulated the transcription of osteoclast‐specific genes, as well as Il‐1β, Il‐6 and Tnf‐α. In addition, TDH inhibited the IKK and NF‐κB signalling pathways and down‐regulated the level of ROS. In vivo studies revealed that TDH improves the bone loss caused by LPS. TDH may be a new candidate or treatment for osteoclast‐associated inflammatory osteolytic disease. Tenacissoside H (TDH) is a monomer extracted from Marsdenia tenacissma and has been shown to be anti‐inflammatory and antioxidant. However, the role of TDH in skeletal diseases remains unclear. In this study, TDH was found to inhibit the IKK/NF‐κB signalling pathway, down‐regulate the expression of c‐FOS, NFATc1, CTSK, and ATP6v0d2, and suppress osteoclast differentiation and function. And TDH could inhibit lipopolysaccharide‐induced transcription of Il1‐β, Il‐6 and Tnf‐α, down‐regulate ROS levels, and In addition, in vivo studies showed that TDH significantly repaired LPS‐induced bone loss. TDH has clinical promise for antiosteoclast activity.
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DOI：
10.1177/15593258211011023
发表时间：
2021-04
期刊：
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影响因子：
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作者：
Lin J;Ruan J;Zhu H;Chen Z;Chen J;Yu H
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