Protection against titanium particle induced osteolysis by cannabinoid receptor 2 selective antagonist
Protection against titanium particle induced osteolysis by cannabinoid receptor 2 selective antagonist
复制标题
大麻素受体 2 选择性拮抗剂对钛颗粒诱导的骨溶解的保护作用
DOI：
10.1016/j.biomaterials.2009.11.069
复制
发表时间：
2010-03-01
期刊：
影响因子：
14
通讯作者：
Wang, Xianbin
中科院分区：
文献类型：
--
作者：
Geng, Dechun;Xu, Yaozeng;Wang, Xianbin
骨溶解和随后的无菌性松动是全关节置换术失败的最常见原因。骨溶解是由磨损碎片引起的炎症反应引起的，导致局部的破骨细胞性种植体周围骨丢失。然而，目前尚无有效的防治假体周围骨溶解的措施。本研究的目的是确定CB2选择性拮抗剂(AM630)是否抑制磨屑诱导的小鼠骨溶解模型中的骨溶解。将钛颗粒引入BALB/c小鼠已建立的气囊中，然后将同基因小鼠的头盖骨植入。在注射钛颗粒前2天，给小鼠腹腔注射AM630，并维持至处死。包括没有接受药物治疗的小鼠，以及只注射生理盐水的小鼠。每组包括10只小鼠。植骨后14天取囊组织进行组织学和分子生物学分析。钛颗粒刺激可显著增加CB2的表达。而AM630治疗组CB2明显减少。AM630可抑制钛颗粒诱导的溶骨相关基因RANK、RANKL和CPK的活性，并抑制钛颗粒刺激的骨囊RANKL的表达。AM630可显著减少小鼠膀胱组织中TRAP+细胞的数量。综上所述，本研究提供了用AM630阻断CB2可显著减少钛颗粒诱导的小鼠气囊模型骨溶解的证据。这一发现表明，CB2选择性拮抗剂，如AM630，可能在预防和治疗磨粒诱导的骨溶解方面具有潜在价值。(C)2009爱思唯尔有限公司。保留所有权利。
Osteolysis and subsequent aseptic loosening are the most common causes of failure of total joint arthroplasty. Osteolysis is initiated by inflammatory response to wear debris, resulting in localized, osteoclastic peri-implant bone loss. However, there were no effective measures for prevention and treatment of periprosthetic osteolysis. The aim of the current study was to determine whether CB2 selective antagonist (AM630) inhibits wear debris-induced osteolysis in a murine osteolysis model. Titanium (Ti) particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. AM630 was given to mice intraperitoneally 2 days before Ti particles introduction and maintained until the sacrifice of the mice. Mice without drug treatment, as well as mice injected with saline alone, were included. Each group contains 10 mice. Pouch tissues were harvested 14 days after bone implantation for histological and molecular analysis. Ti particles stimulation significantly increased CB2 expression. However, less CB2 was observed in AM630 treatment group. AM630 inhibited Ti particle-induced osteolysis associated gene activity of RANK, RANKL and CPK, and diminished RANKL expression in Ti particle stimulated pouches. AM630 markedly reduced the number of TRAP+ cells in pouch tissues. In conclusion, this study provides the evidence that blockage of CB2 with AM630 can markedly reduce Ti particle induced osteolysis in a murine air pouch model. This finding points to the possibility that CB2 selective antagonists like AM630 may have potential value for prevention and treatment of wear particle induced osteolysis. (C) 2009 Elsevier Ltd. All rights reserved.