Co–Cr–Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: A role for osteocytes in particle-induced inflammation

Wear debris-induced osteolysis is purportedly the limiting problem affecting the long term results of joint arthroplasty. Pathogenic effects of wear debris in peri-implant cells such as macrophages, osteoblasts and osteoclasts have been well studied. In contrast, the effects of wear debris on osteocytes, which make up over 90% of all bone cells, remain unknown. We hypothesized that metal implant debris can induce the pro-inflammatory response in osteocytes. This study demonstrated the effects of cobalt–chromium–molybdenum alloy (Co–Cr–Mo) particles on a well-characterized MLO-Y4 osteocyte cell line. Co–Cr–Mo alloy particle treatment significantly (p < 0.05) up-regulated tumor necrosis factor alpha (TNFα) gene expression after 3 and 6 h and TNFα protein production after 24 h, but down-regulated interleukin-6 (IL-6) gene expression after 6 h. Co–Cr–Mo alloy particle treatment also induced osteocyte apoptosis after 24 h. This apoptotic effect was partially (40%) dependent on TNFα. Therefore, our results suggest that osteocytes play a role in particle-induced inflammation and bone resorption following total joint arthroplasty by inducing pro-inflammatory cytokines and inducing osteocyte apoptosis.