Pitavastatin attenuates monocyte activation in response to orthopedic implant‑derived wear particles by suppressing the NF‑κB signaling pathway

Zhang,Zehua; Dai,Fei; Cheng,Peng; Luo,Fei; Hou,Tianyong; Zhou,Qiang; Xie,Zhao; Deng,Moyuan; Xu,Jian‑Zhong

doi:10.3892/mmr.2015.4306

Pitavastatin attenuates monocyte activation in response to orthopedic implant‑derived wear particles by suppressing the NF‑κB signaling pathway

Authors:
- Zehua Zhang
- Fei Dai
- Peng Cheng
- Fei Luo
- Tianyong Hou
- Qiang Zhou
- Zhao Xie
- Moyuan Deng
- Jian‑Zhong Xu
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Affiliations: Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China, National and Regional United Engineering Laboratory of Tissue Engineering, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Published online on: September 9, 2015 https://doi.org/10.3892/mmr.2015.4306
Pages: 6932-6938

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Abstract

Aseptic loosening secondary to particle‑induced periprosthetic osteolysis is considered to be the primary cause of long‑term implant failure in orthopedic surgery. Implant‑derived wear particles activate and recruit macrophages and osteoclasts, which cause a persistent inflammatory response with bone destruction that is followed by a loosening of the implant. Thus, strategies for inhibiting macrophage and osteoclast function may provide a therapeutic benefit for preventing aseptic loosening. The aim of the present study was to determine the effects of pitavastatin on the activation and cytokine response of polymethyl methacrylate (PMMA) particle‑induced monocytes. Peripheral blood monocytes were obtained and treated with PMMA and pitavastatin. ELISA demonstrated that pitavastatin inhibited mRNA and protein expression of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α. Western blot analysis and immunofluorescence staining demonstrated that pitavastatin downregulated inhibitor of κB phosphorylation and degradation, and nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) p65 translocation. Together, these results indicate that pitavastatin may attenuate monocyte activation in response to orthopedic implant wear particles by suppression of the NF‑κB signaling pathway.

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