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.
Highlights
total hip arthroplasty (THA) is one of the most effective procedures for treating severe trauma, rheumatoid arthritis, osteoarthritis and other end-stage joint diseases[1,2,3]
We evaluated our hypothesis by means of synovial samples collected from patients with revision total hip arthroplasty (rTHA) and hip osteoarthritis (hOA), fibroblasts and a novel rat model of femoral head replacement
H&E staining revealed that inflammatory cells infiltrated into the synovial tissue of patients with hOA (Fig. 1b, panels a, e)
Summary
THA is one of the most effective procedures for treating severe trauma, rheumatoid arthritis, osteoarthritis and other end-stage joint diseases[1,2,3]. Wear debris that separate from the surface of prostheses is a primary contributor to aseptic loosening[7,8]. There have always been concerns about polyethylene wear debris-induced aseptic loosening and osteolysis[9,10,11,12]. Early CoC prostheses had a higher revision rate due to poor designs, inadequate material properties, and imperfect surgical techniques. The following complications related to CoC prosthesis have been observed: ceramic fracture, rupture of the prosthesis during operation, liner chipping on insertion, liner canting or dissociation, edge loading, squeaking and aseptic loosening of the prosthesis. Aseptic loosening of CoC bearings during 1970s and 1980s were mainly due to the method of fixation of the components rather than a biological reaction to wear debris[15,16,17,18]. Histological staining has identified ceramic wear particles within individual macrophages in peri-prosthetic tissues, and these particles did not generate serious foreign body granulomas[15]
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