title: Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model.
abstract: 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.
authors.affiliation: 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, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Gazi Jased
authors.initials: GJ
authors.lastname: Ahmed
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences , 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Tatsukawa
authors.affiliation: 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, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences , 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Prosthodontics, Kagoshima University Graduate School , 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Suehiro
authors.affiliation: Graduate School of Environmental Studies, Tohoku University , 6-6-20, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kamitakahara
authors.affiliation: Graduate School of Environmental Studies, Tohoku University , 6-6-20, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Yokoi
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences , 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.affiliation: Departments of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
authors.affiliation: Department of Prosthodontics, Kagoshima University Graduate School , 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences , 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
keywords: beta-tricalcium phosphate; cathepsin K; foreign body giant cell; macrophage; osteoclast