内源性大麻素系统对鼠颅颌骨表型的影响。

Impact of the endocannabinoid system on murine cranial and alveolar bone phenotype.

机构信息

Department of Orthodontics, Medical Faculty, University of Bonn, Welschnonnenstr.17, D-53111 Bonn, Germany.

Endowed Professorship for Oral Medical Technology, University of Bonn, Welschnonnenstr. 17, D-53111 Bonn, Germany.

出版信息

Ann Anat. 2020 Jul;230:151516. doi: 10.1016/j.aanat.2020.151516. Epub 2020 Mar 30.

DOI:10.1016/j.aanat.2020.151516

PMID:32240731

Abstract

PURPOSE

The endocannabionoid signaling system has been demonstrated to be present in the skeleton, with involvement in the regulation of skeletal homeostasis. However, investigations substantiating these findings in cranial and alveolar bones are missing to date. The aim of our study was to investigate a potential impact of the endocannabinoid system on cranial and alveolar bone structures and phenotypes.

BASIC PROCEDURES

CB1, CB2 and WT mice (n = 5) were scanned via μCT. Reconstructed datasets were processed for analyses. Cranial cephalometric measurements were performed with OnyxCephsoftware. Alveolar bone densities were determined via mean grey value measurements with Mimics research 18.0. Alveolar bone heights around teeth in upper and lower jaws were morphometrically analyzed. Alveolar osteoclasts were quantified via TRAP staining of paraffin-embedded histologies. Bone-marrow derived macrophages isolated from murine hind legs were analyzed for CD40 and MMR expression via flow cytometry.

MAIN FINDINGS

CB2 mice exhibited significantly higher bone densities with mean grey values of 138.3 ± 22.6 compared to 121.9 ± 9.3 for WT for upper jaws, and 134.6 ± 22.9 compared to 116.1 ± 12.9 for WT 134.6 ± 22.9. Concurrently, CB2 receptor knockout entailed reduced alveolar bone heights of about 50% compared to WT mice. Antigen-presenting cell marker expression of MMR was significantly diminished in bone-marrow derived macrophages of CB2 mice. Cranium dimensions as much as alveolar osteoclasts were unaffected by receptor knockouts.CB1 receptor knockout did not involve statistically significant alterations in the parameters investigated compared to WT mice.

PRINCIPAL CONCLUSIONS

The endoncannabinoid system, and particularly CB2 receptor strongly affects murine alveolar bone phenotypes. These observations suggest CB2 as promising target in the modulation of oral bone phenotypes, probably by impact on bone dynamics via osteal immune cells.

摘要

目的

内源性大麻素信号系统已被证明存在于骨骼中，参与骨骼内稳态的调节。然而，目前还缺乏关于颅面骨和牙槽骨的研究。本研究旨在探讨内源性大麻素系统对颅面骨结构和表型的潜在影响。

基本程序

使用 μCT 对 CB1、CB2 和 WT 小鼠（n=5）进行扫描。使用 OnyxCeph 软件对重建数据集进行处理和分析。进行颅面头影测量。使用 Mimics research 18.0 测量牙槽骨密度。对上下颌牙齿周围的牙槽骨高度进行形态学分析。通过对石蜡包埋组织进行 TRAP 染色来定量牙槽骨破骨细胞。通过流式细胞术分析从鼠后腿分离的骨髓源性巨噬细胞中 CD40 和 MMR 的表达。

主要发现

CB2 小鼠的骨密度明显较高，上颌骨的平均灰度值为 138.3±22.6，而 WT 小鼠为 121.9±9.3；下颌骨的平均灰度值为 134.6±22.9，而 WT 小鼠为 116.1±12.9。同时，CB2 受体敲除导致牙槽骨高度降低约 50%。CB2 小鼠骨髓源性巨噬细胞中抗原呈递细胞标志物 MMR 的表达显著降低。颅骨尺寸和牙槽骨破骨细胞均不受受体敲除的影响。与 WT 小鼠相比，CB1 受体敲除在研究参数方面没有统计学意义的变化。