G‑CSF delays tooth extraction socket bone healing via the inhibition of bone turnover in mice

Oshitani,Masayuki; Takaoka,Kazuki; Ueta,Miho; Tomimoto,Kohei; Hattori,Hirokazu; Yoneda,Naomichi; Yamanegi,Koji; Noguchi,Kazuma; Kishimoto,Hiromitsu

doi:10.3892/etm.2023.11803

G‑CSF delays tooth extraction socket bone healing via the inhibition of bone turnover in mice

Authors:
- Masayuki Oshitani
- Kazuki Takaoka
- Miho Ueta
- Kohei Tomimoto
- Hirokazu Hattori
- Naomichi Yoneda
- Koji Yamanegi
- Kazuma Noguchi
- Hiromitsu Kishimoto
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Affiliations: Department of Oral and Maxillofacial Surgery, Hyogo Medical University, Nishinomiya, Hyogo 663‑8501, Japan, Department of Pathology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo 663‑8501, Japan
Published online on: January 20, 2023 https://doi.org/10.3892/etm.2023.11803
Article Number: 104

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Abstract

Granulocyte colony‑stimulating factor (G‑CSF) regulates the survival, proliferation and differentiation of all cells in the neutrophil lineage, and is consequently used for neutropenic conditions. Upon G‑CSF administration, osteoblasts and osteocytes are suppressed, and the support system allowing hematopoietic stem cells to remain in the microenvironment is diminished. The present study focused on and investigated G‑CSF as a regulatory factor of bone remodeling. The aim of the present study was to investigate the effect of G‑CSF administration on the bone healing of tooth extraction sockets. Significant differences in the bone volume fraction, and trabecular separation of the proximal femurs and alveolar septa were observed between the G‑CSF and control (saline‑treated) groups. The trabecular bone of the femur and alveolar septa was reduced in the G‑CSF group compared with that in the control group. In addition, serum procollagen type 1 N‑terminal propeptide levels, a marker of bone formation, were lower in the G‑CSF group compared with in the control group. Fibrous connective tissues and immature bone were observed in the extraction socket, and bone healing was delayed in the G‑CSF group compared with that in the control group. The bone area in the extraction socket 6 days after tooth extraction was significantly smaller in the G‑CSF group (23.6%) than that in the control group (45.1%). Furthermore, G‑CSF administration reduced the number of canaliculi per osteocyte and inhibited the connection of osteocyte networks. Consequently, osteoblast activation was inhibited and bone remodeling changed to a state of low bone turnover in the G‑CSG group. Analysis of bone formation parameters revealed that the G‑CSF group exhibited a lower mineral apposition rate compared with in the control group. In conclusion, these findings indicated that G‑CSF may delay bone healing of the socket after tooth extraction.

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