Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, Jiangsu 215006, PR China.
Biomaterials. 2010 Mar;31(8):1996-2000. doi: 10.1016/j.biomaterials.2009.11.069. Epub 2009 Dec 9.
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.
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。骨溶解是由对磨损碎片的炎症反应引起的，导致局部、破骨细胞性植入物周围骨丢失。然而，目前还没有有效的预防和治疗假体周围骨溶解的措施。本研究旨在确定 CB2 选择性拮抗剂（AM630）是否能抑制磨损颗粒诱导的鼠骨溶解模型中的骨溶解。将钛（Ti）颗粒引入 BALB/c 小鼠已建立的气囊中，然后植入同基因同窝仔鼠的颅骨。在 Ti 颗粒引入前 2 天，通过腹腔内给予 AM630，并持续至处死小鼠。包括未接受药物治疗的小鼠以及单独注射生理盐水的小鼠。每组包含 10 只小鼠。在骨植入后 14 天采集气囊组织进行组织学和分子分析。Ti 颗粒刺激显著增加了 CB2 的表达。然而，在 AM630 治疗组中观察到的 CB2 较少。AM630 抑制了 Ti 颗粒诱导的破骨细胞分化基因活性 RANK、RANKL 和 CPK，并减少了 Ti 颗粒刺激气囊中的 RANKL 表达。AM630 明显减少了气囊组织中 TRAP+细胞的数量。总之，这项研究提供了证据表明，用 AM630 阻断 CB2 可以显著减少鼠气囊模型中 Ti 颗粒诱导的骨溶解。这一发现表明，像 AM630 这样的 CB2 选择性拮抗剂可能具有预防和治疗磨损颗粒诱导的骨溶解的潜在价值。
