Abstract
High Crosslink process was introduced in the development of joint prosthetic devices, in order to decrease the wear rate of ultrahigh molecular weight polyethylene (UHMWPE), but it also triggers the formation of free radicals and oxidative stress, which affects the physiological bone remodeling, leading to osteolysis. Vitamin E stabilization of UHMWPE was proposed to provide oxidation resistance without affecting mechanical properties and fatigue strength. The aim of this study is to evaluate the antioxidant effect of vitamin E added to UHMWPE on oxidative stress induced osteolysis, focusing in particular on the oxidative stress response in correlation with the production of osteoimmunological markers, Sclerostin and DKK-1, and the RANKL/OPG ratio compared to conventional UHMWPE wear debris. Human osteoblastic cell line SaOS2 were incubated for 96 h with wear particles derived from crosslinked and not crosslinked Vitamin E-stabilized, UHMWPE without Vitamin E, and growth medium as control. Cellular response to oxidative stress, compared to not treat cells, was evaluated in terms of proteins O-GlcNAcylation, cellular levels of OGA, and OGT proteins by immunoblotting. O-GlcNAcylation and its positive regulator OGT levels are increased in the presence of Vitamin E blended UHMWPE, in particular with not crosslinked Vit E stabilized UHMWPE. Conversely, the negative regulator OGA increased in the presence of UHMWPE not blended with Vitamin E. Vitamin E-stabilized UHMWPE induced a decrease of RANKL/OPG ratio compared to UHMWPE without Vitamin E, and the same effect was observed for Sclerostin, while DKK-1 was not significantly affected. In conclusion, Vitamin E stabilization of UHMWPE increased osteoblast response to oxidative stress, inducing a cellular mechanism aimed at cell survival. Vitamin E antioxidant effect influences the secretion of osteoimmunological factors, shifting the bone turnover balance toward bone protection stimuli. This suggests that Vitamin E-Stabilization of UHMWPE could contribute to reduction of oxidation-induced osteolysis and the consequent loosening of the prosthetic devices, therefore improving the longevity of total joint replacements.
Highlights
One of the main problems in total hip arthroplasty is osteolysis triggered by ultrahigh molecular weight polyethylene (UHMWPE) wear particles [1] and different strategies have been developed to improve the oxidation and wear resistance.High crosslink process was developed in order to decrease the wear rate of UHMWPE [2], but it triggers the formation of free radicals [3], leading to oxidative degradation of the material through a cascade reaction with oxygen [4]
In order to determine whether the observed variation in O-GlcNAC levels was caused by an alteration of the ratio between the two O-GlcNAc cycling enzymes, we examined protein expression of OGA and O-GlcNAc transferase (OGT) by western blot analysis (Figures 2A,B)
As shown in Panel A, a significant increase (p < 0.01) of OGT protein level was found in the presence of not-crosslinked Vitamin E blended UHMWPE, whereas a significant increase (p < 0.05) of OGA enzyme was observed in Vitamin E absence
Summary
High crosslink process was developed in order to decrease the wear rate of UHMWPE [2], but it triggers the formation of free radicals [3], leading to oxidative degradation of the material through a cascade reaction with oxygen [4]. In order to reduce oxidation, Vitamin E was introduced in UHMWPE stabilization, to provide oxidation resistance without affecting mechanical and fatigue strength of the material [5, 6]. Oxidative stress activates the differentiation of osteoclasts from their precursors, while inducing osteoblasts apoptosis, shifting the balance toward osteoclastogenesis and bone resorption [9]. High levels of ROS reduce osteoblast differentiation and activity, reducing mineralization and bone mass [10, 11]. Antioxidant may contribute to osteoblasts differentiation and activity, promoting bone formation [9, 11]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call