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Updated: Dec 28, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Quercetin inhibits macrophage polarization through the p-38α/β signalling pathway and regulates OPG/RANKL balance in
Yu-Wei Ge1, Kai Feng1,2, Xiao-Liang Liu1
1Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
Abstract:
Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle-mediated macrophage polarization, inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p-38α/β signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p-38α/β RNA. We used enzyme-linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro-inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by μ-CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro-inflammatory factors were released. Titanium particle-mediated M1 macrophage polarization, which caused the release of pro-inflammatory factors through the p-38α/β signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.
Insights
Quercetin can suppress titanium particle-induced M1 macrophage polarization and osteolysis, offering a potential therapeutic target for aseptic loosening after hip replacement surgery.
Area of Science:
- Biomaterials Science
- Immunology
- Orthopedic Surgery
Background:
- Aseptic loosening due to wear particles is a major complication of total hip arthroplasty.
- Macrophage polarization plays a critical role in wear particle-induced osteolysis.
Purpose of the Study:
- To investigate the effect of quercetin on wear particle-mediated macrophage polarization, inflammatory response, and osteolysis.
- To explore quercetin as a potential therapeutic agent for aseptic loosening.
Main Methods:
- In vitro studies using RAW264.7 cells and titanium (Ti) particles.
- In vivo studies in a mouse skull model.
- Analysis of macrophage polarization (M1/M2), inflammatory factors, osteoclast differentiation, and osteolysis.
- Utilized flow cytometry, immunofluorescence, ELISA, μ-CT, H&E staining, and immunohistochemistry.
Main Results:
- Ti particles induced M1 macrophage polarization via the p-38α/β signaling pathway.
- M1 macrophages released pro-inflammatory factors, disrupting OPG/RANKL balance and promoting osteoclastogenesis.
- Quercetin suppressed M1 polarization, increased M2 polarization, and mitigated osteolysis both in vitro and in vivo.
- Patient samples showed M1 macrophage accumulation around wear particles.
Conclusions:
- Titanium particle-induced M1 macrophage polarization contributes to osteolysis by releasing pro-inflammatory factors through the p-38α/β pathway.
- Quercetin demonstrates potential as a therapeutic agent to counteract wear particle-induced osteolysis.
- Macrophage polarization is a promising therapeutic target for managing aseptic loosening in total hip arthroplasty.
