Nepetin inhibits osteoclastogenesis by inhibiting RANKL-induced activation of NF-κB and MAPK signalling pathway, and autophagy.
Nepetin inhibits osteoclastogenesis by inhibiting RANKL-induced activation of NF-κB and MAPK signalling pathway, and autophagy.
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DOI：
10.1111/jcmm.16055
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发表时间：
2020-12
影响因子：
5.3
通讯作者：
Hong Z
中科院分区：
文献类型：
--
作者：
Chu B;Chen S;Zheng X;Ye J;Cheng X;Zhang L;Guo D;Wang P;Hong D;Hong Z
磨损颗粒引起的炎性骨溶解导致假体无菌性松动是人工关节置换术失败的主要原因。炎症反应和促骨细胞因子的产生导致破骨细胞形成增加，过度活动导致骨-植入物界面周围广泛的骨破坏。在此，我们发现，具有抗炎和抗增殖特性的天然生物活性黄酮类化合物荆芥素在体外有效抑制RANKL诱导的破骨细胞分化、形成和骨吸收，并在体内保护小鼠免受钛颗粒诱导的颅骨骨质溶解的有害影响。从机制上讲，荆芥素减弱了RANKL诱导的NF-κB和MAPK信号通路活化以及Beclin 1的TRAF 6依赖性泛素化，这是诱导自噬所必需的。简而言之，我们的研究证明了奈哌丁对破骨细胞介导的溶骨性疾病的潜在治疗应用。
Aseptic prosthetic loosening due to wear particle–induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro‐osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extensive bone destruction around the bone‐implant interface. Here we showed that Nepetin, a natural bioactive flavonoid with proven anti‐inflammatory and anti‐proliferative properties, potently inhibited RANKL‐induced osteoclast differentiation, formation and bone resorption in vitro, and protected mice against the deleterious effects of titanium particle–induced calvarial osteolysis in vivo. Mechanistically, Nepetin attenuated RANKL‐induced activation of NF‐κB and MAPK signalling pathways and TRAF6‐dependent ubiquitination of Beclin 1 which is necessary for the induction of autophagy. In brief, our study demonstrates the potential therapeutic application of Nepetin against osteoclast‐mediated osteolytic diseases.
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影响因子：
3.8
作者：
Park JH;Lee NK;Lee SY
通讯作者：
Lee SY
DOI：
10.1084/jem.190.12.1741
发表时间：
1999-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arai F;Miyamoto T;Ohneda O;Inada T;Sudo T;Brasel K;Miyata T;Anderson DM;Suda T
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Suda T
影响因子：
4.8
作者：
Armstrong, AP;Tometsko, ME;Dougall, WC
通讯作者：
Dougall, WC
影响因子：
4.3
作者：
Khan, Mohammad R.;Mordan, Nicola;Brett, Peter M.
通讯作者：
Brett, Peter M.
DOI：
10.1039/c4tb01005a
发表时间：
2014-11-07
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Pajarinen J;Lin TH;Sato T;Yao Z;Goodman SB
通讯作者：
Goodman SB