Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway.

Zige Liu,Jiahao Yang,Guorui Song,Desheng Chen,Yan Li,Chen Zhang,Fengying Guo,Marietta Herrmann

doi:10.1155/2020/1926947

Abstract

Peri-implant osteolysis (PIO) and the subsequent aseptic loosening are the main reasons for artificial joint implant failure. Existing methods for treating aseptic loosening are far from satisfactory, necessitating advanced drug exploration. This study is aimed at investigating the effect and underlying mechanism of tetrandrine (Tet) on inflammatory osteolysis. We established a Ti particle-induced inflammatory osteolysis mouse model and administered Tet or an equal volume of phosphate-buffered saline (PBS). Two weeks later, specimens were collected. Histological staining showed that Tet administration inhibited Ti-stimulated osteolysis. Tartrate-resistant acid phosphate (TRAP) staining and transmission electron microscopy (TEM) demonstrated that osteoclast formation was remarkably inhibited in the groups treated with Tet in a dose-dependent manner. In addition, relevant inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) were also significantly reduced in the calvaria of the Tet-treated groups. Exposure of receptor activator for nuclear factor-κB ligand- (RANKL-) induced bone marrow-derived macrophages (BMMs) and RAW264.7 cells to Tet significantly reduced osteoclast formation, F-actin ring formation, bone resorption, and the expression of relevant genes (matrix metallopeptidase 9 (MMP-9), TRAP, and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1)) during osteoclastogenesis in vitro. Mechanistic studies using Western blotting demonstrated that Tet inhibited the nuclear factor (NF)-κB signaling pathway by decreasing the phosphorylation of inhibitor of NF-κB α (IκBα) and p65, which play important roles in osteoclast formation. Collectively, our data indicate that Tet suppressed Ti-induced inflammatory osteolysis and osteoclast formation in mice, suggesting that Tet has the potential to be developed to treat and prevent wear particle-induced inflammatory osteolysis.

Highlights

Artificial joint replacement is recognized as an effective method for treating various end-stage joint diseases [1]
Abundant epidemiological evidence demonstrates that osteolysis and aseptic loosening around the prosthesis are predominantly attributable to the inflammation caused by the wear particles generated by repeated movement between prosthetic components [2,3,4]
Wozniak et al [5] showed that the elevated levels of nitric oxide (NO) and other inflammatory factors produced by neutrophils may be important in the loosening of the joint prosthesis

Summary

Introduction

Artificial joint replacement is recognized as an effective method for treating various end-stage joint diseases [1]. Abundant epidemiological evidence demonstrates that osteolysis and aseptic loosening around the prosthesis are predominantly attributable to the inflammation caused by the wear particles generated by repeated movement between prosthetic components [2,3,4]. Wozniak et al [5] showed that the elevated levels of nitric oxide (NO) and other inflammatory factors produced by neutrophils may be important in the loosening of the joint prosthesis. Macrophages activated by wear particles secrete various proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 [3, 6]. The concept of “osteoimmunology” has been recognized by many researchers [7].

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Conclusion