The effects of Vitamin E and Polyethylene wear particles on osteocytes <em>in vitro</em>: implications for periprosthetic osteolysis — ASN Events

The effects of Vitamin E and Polyethylene wear particles on osteocytes in vitro: implications for periprosthetic osteolysis (#189)

Renee T Ormsby 1 , Kunihiro Hosaka 1 , Tania Crotti 1 , David Haynes 1 , Andreas Evdokiou 1 , Bogdan Solomon 1 , David Findlay 1 , Gerald J Atkins 1
  1. Biomedical Orthopaedic Research Group, Centre for Orthopaedic and Trauma Research, University of Adelaide, Adelaide, SA, Australia

Total hip replacement surgery is a common procedure that alleviates joint pain and restores movement. Polyethylene (PE) liners commonly serve as the bearing surface of implant prostheses. However, wear of the PE liner can occur through mechanical friction, as well as through oxidation. Newer designed polyethylene liners are imbued with vitamin E, a naturally occurring antioxidant, to prevent oxidative degradation of the PE. Production of PE wear particles has been shown to associate with the formation of periprosthetic osteolytic lesions, which are a major cause of implant (aseptic) loosening. We have shown that osteocytes, the major cell type in the bone, respond to PE particles in vitro by inducing osteocytic osteolysis related genes (MMP13, Cathepsin K, CA2), and promoting osteoclastic bone resorption by upregulating the RANKL:OPG ratio [1]. In this study we investigated potential interactions between osteocytes co-treated with PE wear particles and vitamin E.

Human osteoblasts were differentiated into osteocyte-like cells over 28d, until the cells reached a mature osteocyte-like phenotype. The cells were then overlaid with a collagen gel containing ultra-high molecular weight PE particles (UHMWPE; Ceridust) in the presence or absence of the vitamin E analogues α-Tocopherol or γ-Tocotrienol, and cultured for a further 21d.

PE particles upregulated mRNA expression of osteocytic-osteolysis related genes (MMP13, CA2, CTSK). Addition of either α-Tocopherol or γ-Tocotrienol alone, as well as in combination with PE particles, also resulted in significant upregulation of these genes. PE particles upregulated the pro-osteoclastogenic ratio RANKL:OPG [1], however this was significantly decreased by both vitamin E analogues. All treatments upregulated key antioxidant enzymes SOD1, SOD2 and Catalase, which are important for regulating oxidative stress. These findings suggest that release of Vitamin E, either free or attached to wear particles, could play a role in the development of osteolysis and potentially contribute to implant loosening.

  1. [1] Ormsby RT, Cantley M, Kogawa M, Solomon LB, Haynes DR, Findlay DM, et al. Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis. Acta biomaterialia. 2016;33:242-51.