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Cell Death Dis. 2018 Aug 6;9(8):840. doi: 10.1038/s41419-018-0862-9.

Nano-sized Al2O3 particle-induced autophagy reduces osteolysis in aseptic loosening of total hip arthroplasty by negative feedback regulation of RANKL expression in fibroblasts.

Author information

1
Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2
Department of Orthopedic Surgery, Sun Yat-Sen memorial hospital affiliated to Sun Yat-Sen university, Guangzhou, China.
3
Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. xlzhang@sibs.ac.cn.
4
Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. shenlei@xinhuamed.com.cn.
5
Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. chenxiaodong@xinhuamed.com.cn.

Abstract

Aseptic loosening is mainly caused by wear debris generated by friction that can increase the expression of receptor activation of nuclear factor (NF)-κB (RANKL). RANKL has been shown to support the differentiation and maturation of osteoclasts. Although autophagy is a key metabolic pathway for maintaining the metabolic homeostasis of cells, no study has determined whether autophagy induced by Al2O3 particles is involved in the pathogenesis of aseptic loosening. The aim of this study was to evaluate RANKL levels in patients experiencing aseptic loosening after total hip arthroplasty (THA) and hip osteoarthritis (hOA) and to consequently clarify the relationship between RANKL and LC3II expression. We determined the levels of RANKL and autophagy in fibroblasts treated with Al2O3 particles in vitro while using shBECN-1 interference lentivirus vectors to block the autophagy pathway and BECN-1 overexpression lentivirus vectors to promote autophagy. We established a novel rat model of femoral head replacement and analyzed the effects of Al2O3 particles on autophagy levels and RANKL expression in synovial tissues in vivo. The RANKL levels in the revision total hip arthroplasty (rTHA) group were higher than those in the hOA group. In patients with rTHA with a ceramic interface, LC3II expression was high, whereas RANKL expression was low. The in vitro results showed that Al2O3 particles promoted fibroblast autophagy in a time- and dose-dependent manner and that RANKL expression was negatively correlated with autophagy. The in vivo results further confirmed these findings. Al2O3 particles induced fibroblast autophagy, which reduced RANKL expression. Decreasing the autophagy level promoted osteolysis and aseptic prosthetic loosening, whereas increasing the autophagy level reversed this trend.

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