The most prominent fibroblasts responses to implant wear debris were MMP-1, MCP-1, IL-1β, IL-6, IL-8, cyclooxygenase 1 (cox-1), cox-2, leukemia inhibitory factor, transforming growth factor beta 1, and TGFβ receptor type I. Additionally, downregulation of bone maintenance regulator such as osteoprotegrin (OPG) has been reported to decrease in osteoblasts/soft tissue cells exposed to implant debris and may contribute to regulatory RANKL/OPG imbalance in bone homeostasis contributing to the pathogenesis of implant debris-associated aseptic loosening/bone loss (53). Here, PTGS1 is linked to aseptic loosening.