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.

译文

大麻素受体及其配体在调节骨代谢中起重要作用。先前对1型大麻素受体缺陷小鼠的研究表明,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型大麻素受体缺乏症 (Cnr2 (-/-)) 小鼠骨骼表型的影响。我们研究了CD1背景下的Cnr2 (-/-) 小鼠,并将发现与先前在Cnr2 (-/-) C57BL/6小鼠中报道的结果进行了比较。与野生型 (WT) 相比,年轻的雌性Cnr2 (-/-) CD1小鼠的骨转换低,小梁骨量高,与Cnr2 (-/-) C57BL/6小鼠的情况相反,据报道小梁骨量与WT相似。Cnr2 (-/-) CD1小鼠由于骨形成减少,随着年龄的增长,胫骨的小梁骨损失比WT多,并且在12个月时,基因型之间的小梁骨体积没有差异。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,骨量增加,骨量减少。在雄性小鼠中,Cnr2 (-/-) 和WT之间的骨骼表型没有实质性差异。两种性别的Cnr2 (-/-) 和WT小鼠的皮质骨表型相似。Cnr2缺乏对骨骼有位点和性别特异性影响,主要影响小梁骨,小梁骨受小鼠品系之间遗传差异的影响。对负责途径的进一步评估可能会对大麻素受体调节骨代谢的机制产生新的见解。

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