The Effects of Vitamin E Analogues α-Tocopherol and γ-Tocotrienol on the Human Osteocyte Response to Ultra-high Molecular Weight Polyethylene Wear Particles

Abstract BackgroundPolyethylene (PE) liners are a common bearing surface of orthopaedic prostheses. In some products, vitamin E is added to PE as a preventive measure against oxidative degradation. Ultra-high molecular weight PE (UHMWPE) wear particles contribute to periprosthetic osteolysis, a major cause of aseptic loosening. Osteocytes are an important cell type for controlling both bone mineralisation and bone resorption, and respond to UHMWPE particles by inducing both osteocytic osteolysis and support of osteoclastogenesis. Here, we examined the effects of the vitamin E analogues α-tocopherol and γ-tocotrienol alone or in the context of wear particles on human osteocyte gene expression and mineralisation behaviour. MethodsHuman primary osteoblasts isolated from patients undergoing hip arthroplasty were differentiated for 28d to an osteocyte-like stage. Cultures were exposed to UHMWPE wear particles in the presence or absence of either α-Tocopherol or γ-Tocotrienol. Gene expression related to the oxidative response, osteocytic osteolysis and osteoclastogenesis was measured by real-time RT-PCR. The effect on calcium release from mineralised osteocyte-like cultures was also measured. ResultsBoth α-Tocopherol and γ-Tocotrienol upregulated expression of several antioxidant-related genes. UHMWPE particles also upregulated antioxidant gene expression, suggesting the involvement of oxidative stress pathways. UHMWPE particles upregulated the pro-osteoclastogenic RANKL:OPG mRNA ratio, however, this was reduced in the presence of vitamin E analogues. UHMWPE particles also upregulated mRNA expression of osteocytic-osteolysis related genes. However, treatment with either analogue alone and in combination with UHMWPE particles also resulted in significant upregulation of these genes. Consistent with this, both vitamin E analogues promoted calcium release from mineralised cultures of osteocyte-like cells. DiscussionOur findings suggest that vitamin E analogues may suppress osteocyte support of osteoclastogenesis in response to UHMWPE particle exposure. Vitamin E analogues exert an antioxidant effect on osteocytes, however, this appears to involve the induction of osteocytic osteolysis, which could promote periprosthetic osteolysis. It will be important to further elucidate the effects of vitamin E on the cells of the prosthetic joint in order to understand the potential effects of their inclusion in prosthetic materials.