Wear Debris Inhibition of Anti-Osteoclastogenic Signaling by Interleukin-6 and Interferon- : Mechanistic Insights and Implications for Periprosthetic Osteolysis

Abstract

Titanium inhibits both interferon-gamma and interleukin-6 signaling in human osteoclast precursor cells, whereas polymethylmethacrylate bone cement inhibits only the latter. Wear particle inhibition of interleukin-6 specifically involves the activation of p38 mitogen-activated protein kinase and is accompanied by substantial induction of SOCS3, an inhibitor of interleukin-6 signaling. In contrast, titanium inhibition of interferon-gamma signaling is not dependent on mitogen-activated protein kinase activation and is accompanied by only modest induction of the interferon-gamma inhibitor SOCS1.