Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model

  • Ahmed Gazi Jased
    Departments of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences
  • Tatsukawa Eri
    Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences
  • Morishita Kota
    Departments of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences
  • Shibata Yasuaki
    Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences
  • Suehiro Fumio
    Department of Prosthodontics, Kagoshima University Graduate School
  • Kamitakahara Masanobu
    Graduate School of Environmental Studies, Tohoku University
  • Yokoi Taishi
    Graduate School of Environmental Studies, Tohoku University
  • Koji Takehiko
    Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences
  • Umeda Masahiro
    Departments of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences
  • Nishimura Masahiro
    Department of Prosthodontics, Kagoshima University Graduate School
  • Ikeda Tohru
    Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences

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The implantation of biomaterials induces a granulomatous reaction accompanied by foreign body giant cells (FBGCs). The characterization of multinucleated giant cells (MNGCs) around bone substitutes implanted in bone defects is more complicated because of healing with bone admixed with residual bone substitutes and their hybrid, and the appearance of two kinds of MNGCs, osteoclasts and FBGCs. Furthermore, the clinical significance of osteoclasts and FBGCs in the healing of implanted regions remains unclear. The aim of the present study was to characterize MNGCs around bone substitutes using an extraskeletal implantation model and evaluate the clinical significance of osteoclasts and FBGCs. Beta-tricalcium phosphate (β-TCP) granules were implanted into rat subcutaneous tissue with or without bone marrow mesenchymal cells (BMMCs), which include osteogenic progenitor cells. We also compared the biological significance of plasma and purified fibrin, which were used as binders for implants. Twelve weeks after implantation, osteogenesis was only detected in specimens implanted with BMMCs. The expression of two typical osteoclast markers, tartrate-resistant acid phosphatase (TRAP) and cathepsin-K (CTSK), was analyzed, and TRAP-positive and CTSK-positive osteoclasts were only detected beside bone. In contrast, most of the MNGCs in specimens without the implantation of BMMCs were FBGCs that were negative for TRAP, whereas the degradation of β-TCP was detected. In the region implanted with β-TCP granules with plasma, FBGCs tested positive for CTSK, and when β-TCP granules were implanted with purified fibrin, FBGCs tested negative for CTSK. These results showed that osteogenesis was essential to osteoclastogenesis, two kinds of FBGCs, CTSK-positive and CTSK-negative, were induced, and the expression of CTSK was plasma-dependent. In addition, the implantation of BMMCs was suggested to contribute to osteogenesis and the replacement of implanted β-TCP granules to bone.

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