論文

査読有り 国際誌
2020年6月

Effects of N-methyl-d-aspartate receptor antagonist MK-801 (dizocilpine) on bone homeostasis in mice.

Journal of oral biosciences
  • Shuichi Kiyohara
  • ,
  • Nobuhiro Sakai
  • ,
  • Kazuaki Handa
  • ,
  • Tomoyuki Yamakawa
  • ,
  • Koji Ishikawa
  • ,
  • Masahiro Chatani
  • ,
  • Akiko Karakawa
  • ,
  • Yuki Azetsu
  • ,
  • Motohiro Munakata
  • ,
  • Masahiko Ozeki
  • ,
  • Takako Negishi-Koga
  • ,
  • Masamichi Takami

62
2
開始ページ
131
終了ページ
138
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.job.2020.03.003

OBJECTIVES: To gain insight into the role of the N-methyl-d-aspartate (NMDA) receptor in bone metabolism by examining the effects of its noncompetitive antagonist, MK-801 (dizocilpine), on bone homeostasis and bone healing in mice. METHODS: MK-801 (2.5 mg/kg) or saline (in control groups) was intravenously administered to healthy mice and mice with bone-defects daily for seven to 14 days. Bone defects were artificially created in femurs using a drill and reamer. Following euthanasia, bones were extracted and processed for microcomputed tomography (μCT) and histological analyses. The effects of MK-801 on osteoclast differentiation by bone marrow macrophages (BMMs) were examined in vitro. mRNA expressionlevels of Grin3b levels were also examined using reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Bone volume was significantly decreased in mice administered MK-801 for 14 days. Additionally, the number of osteoclasts was reduced, while number of osteoblasts and rate of bone formation were increased in these mice. MK-801 inhibited osteoclast differentiation dose-dependently in vitro. RT-PCR findings suggested expression of Grin3b, a subunit of the NMDA receptor, in BMMs. During the healing process of artificially created defects in femurs, no significant differences were found between the control and MK-801-treated groups, indicating no stimulatory or inhibitory effects by MK-801 administration. CONCLUSIONS: These results indicate that blockade of the NMDA receptor by MK-801 administration affects bone metabolism but not the healing process of artificial bone defects.

リンク情報
DOI
https://doi.org/10.1016/j.job.2020.03.003
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32289529

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