کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1927868 | 1050268 | 2016 | 7 صفحه PDF | دانلود رایگان |
• Autophagy can be activated by TiAl6V4 particles.
• Wear particle-induced TNF-α secretion in macrophages is mediated by autophagy.
• Blocking autophagy effectively attenuated particle-induced osteolysis in vivo.
Peri-prosthetic osteolysis and the consequent aseptic loosening constitute the most common reason for total joint arthroplasty failure and surgical revision. Although numerous studies suggest that pro-inflammatory cytokines induced by wear particles is involved in the pathological process of aseptic loosening, the underlying mechanism linking wear particles to pro-inflammatory cytokines remains to be illustrated. In the present study, we investigated the effect of autophagy on TNF-α secretion induced by TiAl6V4 particles (TiPs) in macrophages and in a calvarial resorption animal model. Our study demonstrated that TiPs activated autophage in macrophages and particle-induced osteolysis animal models as well as periprosthetic membranes of patients with aseptic loosening. The autophagy inhibitor 3-MA (3-methyladenine) could dramatically reduce TiPs-induced TNF-α expression both in macrophages and in membranes from animal models. Furthermore, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Collectively, these results suggest that autophagy plays a key role in TiPs-induced osteolysis by promoting TNF-α expression and that blocking autophagy may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.
Journal: Biochemical and Biophysical Research Communications - Volume 473, Issue 1, 22 April 2016, Pages 133–139