Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway
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 underl...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/1926947 |
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| author | Zige Liu Yan Li Fengying Guo Chen Zhang Guorui Song Jiahao Yang Desheng Chen |
| author_facet | Zige Liu Yan Li Fengying Guo Chen Zhang Guorui Song Jiahao Yang Desheng Chen |
| author_sort | Zige Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-30327b9c9824422f9e0b8c9efc43519c |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-30327b9c9824422f9e0b8c9efc43519c2025-02-03T05:51:15ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/19269471926947Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB PathwayZige Liu0Yan Li1Fengying Guo2Chen Zhang3Guorui Song4Jiahao Yang5Desheng Chen6Department of Orthopedic Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaSchool of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, ChinaSchool of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Orthopedic Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Orthopedic Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaSchool of Clinical Medicine, Shimane University, Shimane 693-8501, JapanDepartment of Orthopedic Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaPeri-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.http://dx.doi.org/10.1155/2020/1926947 |
| spellingShingle | Zige Liu Yan Li Fengying Guo Chen Zhang Guorui Song Jiahao Yang Desheng Chen Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway Mediators of Inflammation |
| title | Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway |
| title_full | Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway |
| title_fullStr | Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway |
| title_full_unstemmed | Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway |
| title_short | Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway |
| title_sort | tetrandrine inhibits titanium particle induced inflammatory osteolysis through the nuclear factor κb pathway |
| url | http://dx.doi.org/10.1155/2020/1926947 |
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