Rheumatic Diseases Unit, Centre for Molecular Medicine, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Calcif Tissue Int. 2014 Mar;94(3):259-68. doi: 10.1007/s00223-013-9793-8. Epub 2013 Sep 14.
Cannabinoid receptors and their ligands play significant roles in regulating bone metabolism. Previous studies of type 1 cannabinoid receptor-deficient mice have shown that genetic background influences the skeletal phenotype. Here, we investigated the effects of genetic background on the skeletal phenotype of mice with type 2 cannabinoid receptor deficiency (Cnr2 (-/-)). We studied Cnr2 (-/-) mice on a CD1 background and compared the findings with those previously reported in Cnr2 (-/-) C57BL/6 mice. Young female Cnr2 (-/-) CD1 mice had low bone turnover and high trabecular bone mass compared with wild-type (WT), contrasting with the situation in Cnr2 (-/-) C57BL/6 mice where trabecular bone mass has been reported to be similar to WT. The Cnr2 (-/-) CD1 mice lost more trabecular bone at the tibia with age than WT due to reduced bone formation, and at 12 months there was no difference in trabecular bone volume between genotypes. This differs from the phenotype previously reported in C57BL/6 Cnr2 (-/-) mice, where bone turnover is increased and bone mass reduced with age. There were no substantial differences in skeletal phenotype between Cnr2 (-/-) and WT in male mice. Cortical bone phenotype was similar in Cnr2 (-/-) and WT mice of both genders. Deficiency of Cnr2 has site- and gender-specific effects on the skeleton, mainly affecting trabecular bone, which are influenced by genetic differences between mouse strains. Further evaluation of the pathways responsible might yield new insights into the mechanisms by which cannabinoid receptors regulate bone metabolism.
大麻素受体及其配体在调节骨代谢中发挥着重要作用。先前对 1 型大麻素受体缺失小鼠的研究表明，遗传背景会影响骨骼表型。在这里，我们研究了遗传背景对 2 型大麻素受体缺失（Cnr2（-/-））小鼠骨骼表型的影响。我们研究了 CD1 背景下的 Cnr2（-/-）小鼠，并将研究结果与先前在 Cnr2（-/-）C57BL/6 小鼠中报道的结果进行了比较。与 Cnr2（-/-）C57BL/6 小鼠的情况相反，年轻雌性 Cnr2（-/-）CD1 小鼠的骨转换率低，骨小梁质量高，而 Cnr2（-/-）C57BL/6 小鼠的骨小梁质量与 WT 相似。随着年龄的增长，Cnr2（-/-）CD1 小鼠的胫骨骨小梁丢失更多，因为骨形成减少，而在 12 个月时，两种基因型的骨小梁体积没有差异。这与先前在 C57BL/6 Cnr2（-/-）小鼠中报道的表型不同，在 C57BL/6 Cnr2（-/-）小鼠中，随着年龄的增长，骨转换率增加，骨量减少。在雄性小鼠中，Cnr2（-/-）和 WT 之间的骨骼表型没有明显差异。在两性 Cnr2（-/-）和 WT 小鼠中，皮质骨表型相似。Cnr2 缺失对骨骼的影响具有部位和性别特异性，主要影响骨小梁，这受不同小鼠品系之间遗传差异的影响。进一步评估相关途径可能会深入了解大麻素受体调节骨代谢的机制。
