Effects of N-methyl-d-aspartate receptor antagonist MK-801 (dizocilpine) on bone homeostasis in mice
| Autor: | Masahiro Chatani, Yuki Azetsu, Kazuaki Handa, Shuichi Kiyohara, Takako Negishi-Koga, Akiko Karakawa, Nobuhiro Sakai, Masamichi Takami, Masahiko Ozeki, Tomoyuki Yamakawa, Koji Ishikawa, Motohiro Munakata |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Artificial bone N-Methylaspartate medicine.drug_class Medicine (miscellaneous) Bone healing Receptors N-Methyl-D-Aspartate General Biochemistry Genetics and Molecular Biology Bone remodeling Mice 03 medical and health sciences 0302 clinical medicine Osteoclast Internal medicine medicine Animals Homeostasis General Dentistry Chemistry X-Ray Microtomography 030206 dentistry Receptor antagonist Dizocilpine 030104 developmental biology medicine.anatomical_structure Endocrinology NMDA receptor Bone marrow Dizocilpine Maleate medicine.drug |
| Zdroj: | Journal of Oral Biosciences. 62:131-138 |
| ISSN: | 1349-0079 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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