Inhibition of EGFR Pathway Suppresses M1 Macrophage Polarization and Osteoclastogenesis, Mitigating Titanium Particle-Induced Bone Resorption

作者：Qiyu Jia, Lu Liu, Yunyuan Yu, Wuhuzi Wulamu, Lin Jia, Bo Liu, Hao Zheng, Zhenlei Peng, Xiaogang Zhang, Ruixian Zhu · 发表于：Journal of Inflammation Research · 年份：2024 · DOI：10.2147/jir.s484529 · 被引用次数：13 · 研究领域：Bone Tissue Engineering Materials、Orthopaedic implants and arthroplasty、Bone Metabolism and Diseases

Purpose: The polarization of macrophages towards the pro-inflammatory M1 phenotype and osteoclast overactivation play a significant role in the pathogenesis of aseptic loosening of orthopedic implants. This study sought to examine the expression and activation of macrophages and osteoclasts in implant biopsies with respect to epidermal growth factor receptor (EGFR) signaling and to assess the potential of EGFR inhibition in mitigating titanium particle-induced bone resorption in a cranial resorption murine model. Methods: Bone marrow-derived macrophages (BMDMs) were stimulated with Tumor Necrosis Factor-alpha (TNF-α) and Interferon-gamma (IFN-γ) initially. Subsequently, Osteoclast differentiation was initiated after Gefitinib was added to the treatment groups. Male C57BL/6 mice were treated with Gefitinib or 0.5% Carboxymethyl Cellulose-Sodium (CMC-Na) by oral gavage daily for two weeks. A sham group received no further intervention, while the other groups had titanium particles implanted. Tissues were collected and analyzed by measurements such as micro-computed tomography (micro-CT) analyses, histology, immunofluorescence stainings, cell viability assays, assays for resorption pit formation, Reverse Transcription-Polymerase Chain Reactions (RT-PCRs), and Western blots were conducted. Results: The study demonstrated a significant upregulation of EGFR in response to titanium particle exposure. Inhibition of EGFR phosphorylation with gefitinib effectively reduced bone degradat...