Kiyohara Shuichi, Sakai Nobuhiro, Handa Kazuaki, Yamakawa Tomoyuki, Ishikawa Koji, Chatani Masahiro, Karakawa Akiko, Azetsu Yuki, Munakata Motohiro, Ozeki Masahiko, Negishi-Koga Takako, Takami Masamichi
Department of Pharmacology, Showa University School of Dentistry, 1-5-8 Hatanodai Shinagawa, Tokyo, 142-8555 Japan; Department of Implant Dentistry, Showa University School of Dentistry, 2-1-1 Kitasenzoku, Ota, Tokyo, 145-8515, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai Shinagawa, Tokyo, 142-8555, Japan.
Department of Pharmacology, Showa University School of Dentistry, 1-5-8 Hatanodai Shinagawa, Tokyo, 142-8555 Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai Shinagawa, Tokyo, 142-8555, Japan.
J Oral Biosci. 2020 Jun;62(2):131-138. doi: 10.1016/j.job.2020.03.003. Epub 2020 Apr 11.
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.
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).
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.
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.
通过研究N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂MK-801（地佐环平）对小鼠骨稳态和骨愈合的影响，深入了解NMDA受体在骨代谢中的作用。
将MK-801（2.5mg/kg）或生理盐水（对照组）每日静脉注射给健康小鼠和有骨缺损的小鼠，持续7至14天。使用钻头和铰刀在股骨上人工制造骨缺损。安乐死后，取出骨骼并进行微计算机断层扫描（μCT）和组织学分析。体外检测MK-801对骨髓巨噬细胞（BMMs）破骨细胞分化的影响。还使用逆转录聚合酶链反应（RT-PCR）检测Grin3b水平的mRNA表达。
给予MK-801 14天的小鼠骨体积显著减少。此外，这些小鼠的破骨细胞数量减少，而成骨细胞数量和骨形成速率增加。MK-801在体外剂量依赖性地抑制破骨细胞分化。RT-PCR结果表明，NMDA受体的一个亚基Grin3b在BMMs中有表达。在股骨人工制造缺损的愈合过程中，对照组和MK-801治疗组之间未发现显著差异，表明给予MK-801没有刺激或抑制作用。
这些结果表明，给予MK-801阻断NMDA受体可影响骨代谢，但不影响人工骨缺损的愈合过程。
