Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption.
Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption.
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新型 V-ATP 酶抑制剂水利苯卤酰胺通过抑制破骨细胞骨吸收来预防磨损颗粒引起的骨溶解
DOI：
10.1371/journal.pone.0034132
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dai KR
中科院分区：
文献类型：
--
作者：
Qin A;Cheng TS;Lin Z;Cao L;Chim SM;Pavlos NJ;Xu J;Zheng MH;Dai KR
磨粒引起的假体周围松动(无菌性假体松动)是全关节置换术最常见的原因之一。众所周知，破骨细胞的广泛骨破坏(骨溶解)是磨损颗粒导致种植体周围松动的原因。因此，抑制破骨细胞性骨吸收可防止磨粒引起的骨溶解，并可能成为治疗假体松动的潜在途径。在这里，我们首次在小鼠颅骨模型中证明了一种新的V-ATPase抑制剂--唾液苯卤胺可以减轻磨粒诱导的骨溶解。体外生化和形态分析显示，抑制骨溶解部分归因于破骨细胞酸化和极化的破坏，这两者都是破骨细胞骨吸收的先决条件。有趣的是，V-κ酶抑制剂还通过抑制RANKL诱导的NF-ERKB和ERK信号通路而损害破骨细胞的分化。综上所述，我们发现唾液苯卤胺影响破骨细胞分化、酸化和极化等多个生理过程，导致体外抑制破骨细胞骨吸收和体内磨损颗粒诱导的骨溶解。研究结果表明，新一代V-ATPase抑制剂，如唾液苯卤胺，是治疗种植体周围骨溶解的潜在抗吸收药物。
Wear particle-induced peri-implant loosening (Aseptic prosthetic loosening) is one of the most common causes of total joint arthroplasty. It is well established that extensive bone destruction (osteolysis) by osteoclasts is responsible for wear particle-induced peri-implant loosening. Thus, inhibition of osteoclastic bone resorption should prevent wear particle induced osteolysis and may serve as a potential therapeutic avenue for prosthetic loosening. Here, we demonstrate for the first time that saliphenylhalamide, a new V-ATPase inhibitor attenuates wear particle-induced osteolysis in a mouse calvarial model. In vitro biochemical and morphological assays revealed that the inhibition of osteolysis is partially attributed to a disruption in osteoclast acidification and polarization, both a prerequisite for osteoclast bone resorption. Interestingly, the V-ATPase inhibitor also impaired osteoclast differentiation via the inhibition of RANKL-induced NF-κB and ERK signaling pathways. In conclusion, we showed that saliphenylhalamide affected multiple physiological processes including osteoclast differentiation, acidification and polarization, leading to inhibition of osteoclast bone resorption in vitro and wear particle-induced osteolysis in vivo. The results of the study provide proof that the new generation V-ATPase inhibitors, such as saliphenylhalamide, are potential anti-resorptive agents for treatment of peri-implant osteolysis.
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影响因子：
8.2
作者：
Chao Zhang;Ting-ting Tang;Ke-rong Dai
通讯作者：
Ke-rong Dai
影响因子：
4.8
作者：
Lee, BS;Gluck, SL;Holliday, LS
通讯作者：
Holliday, LS
影响因子：
4.8
作者：
Huss, M;Ingenhorst, G;Wieczorek, H
通讯作者：
Wieczorek, H
影响因子：
2.8
作者：
Al-Saffar, N;Revell, PA
通讯作者：
Revell, PA
DOI：
10.2106/00004623-199306000-00007
发表时间：
1993-06-01
影响因子：
5.3
作者：
JIRANEK, WA;MACHADO, M;HARRIS, WH
通讯作者：
HARRIS, WH