Pitavastatin attenuates monocyte activation in response to orthopedic implant-derived wear particles by suppressing the NF-κB signaling pathway.
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.
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Zehua
Z
Zhang
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Fei
F
Dai
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Peng
P
Cheng
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Fei
F
Luo
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Tianyong
T
Hou
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Qiang
Q
Zhou
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Zhao
Z
Xie
National and Regional United Engineering Laboratory of Tissue Engineering, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Moyuan
M
Deng
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Jian-Zhong
JZ
Xu
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D010316:Particle Size; D019904:Polymethyl Methacrylate / Q000009:adverse effects*; D019736:Prostheses and Implants / Q000009:adverse effects*; D011804:Quinolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D055815:Young Adult
D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D011804:Quinolines; D019904:Polymethyl Methacrylate; C108475:pitavastatin