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 OnyxCeph3TMsoftware. 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.

中文翻译：

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内源性大麻素系统对小鼠颅骨和牙槽骨表型的影响。

目的已证明内源性大麻素信号系统存在于骨骼中，参与骨骼稳态的调节。然而，迄今为止，尚缺乏证实这些发现的颅骨和牙槽骨研究。我们研究的目的是研究内源性大麻素系统对颅骨和牙槽骨结构和表型的潜在影响。基本程序通过μCT扫描CB1-/-，CB2-/-和WT小鼠（n = 5）。处理重建的数据集以进行分析。使用OnyxCeph3TM软件进行颅脑测量。牙槽骨密度通过Mimics research 18.0的平均灰度值测量确定。分析了上颌和下颌牙齿周围的牙槽骨高度。通过对石蜡包埋的组织学进行TRAP染色，对肺泡破骨细胞进行定量。通过流式细胞术分析从鼠后腿分离的骨髓来源的巨噬细胞的CD40和MMR表达。主要发现CB2-/-小鼠表现出明显更高的骨密度，上颌WT的平均灰度值为138.3±22.6，而WT为121.9±9.3，WT的平均灰度值为134.6±22.9，而WT为136.1±22.9。同时，与野生型小鼠相比，CB2受体基因敲除使肺泡骨高度降低了约50％。在骨髓衍生的CB2-/-小鼠巨噬细胞中，MMR的抗原呈递细胞标志物表达明显减少。颅骨的大小与肺泡破骨细胞一样，不受受体敲除的影响。与WT小鼠相比，CB1受体基因敲除不涉及所研究参数的统计学显着变化。主要结论内源性大麻素系统，尤其是CB2受体强烈影响鼠牙槽骨的表型。这些观察结果表明，CB2是口腔骨表型调节中有希望的靶标，可能是通过骨免疫细胞对骨动力学的影响。