Gene expression analysis of fresh extraction wounds prior to onset of bisphosphonate-related osteonecrosis of the jaw-like lesions in mice: A preliminary animal study
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- Kuroshima Shinichiro
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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- Nakajima Kazunori
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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- Sasaki Muneteru
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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- Hayano Hiroki
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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- Inoue Maaya
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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- Kozutsumi Ryohei
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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- Sawase Takashi
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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<p>Purpose The aim of the present study was to investigate the effects of chemotherapeutic/bisphosphonate combination therapy with tooth extraction on gene expression patterns of fresh extraction wounds during initial stages prior to their diagnosis as bisphosphonate-related osteonecrosis of the jaw (BRONJ)-like lesions in mice.</p><p>Methods Female C57BL/6J mice were used. To create a high-prevalence BRONJ mouse model, combination therapy with the chemotherapy drug cyclophosphamide (CY) and zoledronic acid (ZA) was performed (CY/ZA). Both maxillary first molars were extracted 3 weeks after drug therapy. Saline was used as the control (VC). Soft tissues near the fresh extraction wounds were dissected at 72 h postextraction to investigate the gene expression patterns. Maxillae and long bones at 2 and 4 weeks postextraction were also analyzed.</p><p>Results CY/ZA significantly increased the relative expression levels of IL-6 and decreased those of IL-10 and IGF-1 when compared with those in VC. Moreover, CY/ZA significantly reduced the relative expression levels of CCR-7, cxcl12, cxcr4, and CD105 when compared with those in VC, whereas the level of F4/80 was significantly increased by CY/ZA. Furthermore, CY/ZA significantly decreased the relative expression levels of VEGFA, VEGFB, and VEGFC at 72 h postextraction compared with those in VC.</p><p>Conclusions Considering that the present study lacked adequate in vitro models, CY/ZA markedly changed the gene expression patterns associated with wound healing from the initial stages prior to onset of BRONJ-like lesions, which may help us to understand the pathophysiology of BRONJ in humans.</p>
収録刊行物
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- Journal of Prosthodontic Research
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Journal of Prosthodontic Research 65 (4), 546-553, 2021
公益社団法人 日本補綴歯科学会