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 (CB2) 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 CB2-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 CB2 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 CB2 by AM630 inhibited the titanium particle-induced inflammatory reaction by reducing pro-inflammatory cytokines in vitro and in vivo.