title: Effects of a cannabinoid receptor 2 selective antagonist on the inflammatory reaction to titanium particles in vivo and in vitro.
abstract: Wear particle-induced inflammation is a major factor contributing to aseptic loosening in peri-prosthetic tissue. The effects of cannabinoid receptor 2 (CB(2)) on wear particle-induced inflammation remain unclear. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to assess the effects of a CB(2)-selective antagonist, AM630, on regulation of the inflammatory reaction and production of pro-inflammatory cytokines in response to in vitro and in vivo stimulation with titanium particles. In vitro studies, in a model for pre-osteoclast-like cells, demonstrated that AM630 inactivation of CB(2) profoundly inhibited interleukin (IL)-1β and tumour necrosis factor (TNF)-α production by RAW264.7 cells stimulated with titanium particles. In vivo findings in a murine air-pouch model of titanium-induced inflammatory osteolysis indicated that AM630 reduced titanium-induced tissue inflammation, seen as a reduction in pouch membrane thickness, inflammatory infiltration and levels of the pro-inflammatory cytokines IL-1β and TNF-α. Thus, inactivation of CB(2) by AM630 inhibited the titanium particle-induced inflammatory reaction by reducing pro-inflammatory cytokines in vitro and in vivo.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Jiangsu, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhou
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Mao
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: D
authors.initials: D
authors.lastname: Geng
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020007:Implants, Experimental; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D052638:Particulate Matter / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014025:Titanium / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D007211:Indoles; D053583:Interleukin-1beta; D052638:Particulate Matter; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; C094023:iodopravadoline