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Quantitative analyses of bone composition in acetylcholine receptor M3R and alpha7 knockout mice.

机译:乙酰胆碱受体M3R和alpha7基因敲除小鼠的骨组成的定量分析。

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Increasing collagen synthesis was observed in lung after stimulation of nicotinic and muscarinic acetylcholine receptors (nAChR and mAChR) on fibroblasts. Since collagen synthesis is an important process during fracture healing and bone remodelling, we asked whether cholinergic receptors are involved in bone collagen production.In the present study we analysed 16 week old male knockout mice for nAChRα7 (α7-KO) and mAChR M3R (M3R-KO) in correlation to their corresponding wild types (WT). Microarchitecture of right femora, vertebrae Th13 and L1 were analysed by 3D Micro-CT, left femora by a three-point bending test and humeri by real-time RT-PCR.A significant decrease in relative bone volume, trabecular thickness, trabecular number, bone surface density, and a significant increase in trabecular separation and structure model index were measured for the M3R-KO using Micro-CT analysis. Bending stiffness of M3R-KO was significantly reduced in comparison to WT as well as the collagen 1α1 and 1α2 mRNA expression was down-regulated. No changes were detected for α7-KO using Micro-CT, biomechanical testing, and collagen mRNA expression.Our results indicate that nAChRα7 are not involved in the regulation of bone collagen synthesis whereas M3R exert stimulatory effects on cancellous bone microarchitecture, flexural rigidity, and bone matrix synthesis. Since the M3R-KO exhibit bone structures similar to systemically diseased bone it might be valuable to establish new therapeutic strategies using administration of agonists for the M3R to improve bone qualities.
机译:刺激成纤维细胞上的烟碱和毒蕈碱乙酰胆碱受体(nAChR和mAChR)后,肺中胶原蛋白合成增加。由于胶原蛋白合成是骨折愈合和骨重塑过程中的重要过程,因此我们询问胆碱能受体是否参与骨胶原蛋白的产生。在本研究中,我们分析了16周龄的雄性基因敲除小鼠的nAChRα7(α7-KO)和mAChR M3R(M3R -KO)与其对应的野生型(WT)相关。右股骨,椎骨Th13和L1的微结构通过3D Micro-CT分析,左股骨通过三点弯曲测试进行分析,肱骨通过实时RT-PCR分析。使用Micro-CT分析测量了M3R-KO的骨表面密度以及小梁分离和结构模型指数的显着增加。与WT相比,M3R-KO的弯曲刚度显着降低,并且胶原1α1和1α2mRNA表达下调。使用Micro-CT,生物力学测试和胶原mRNA表达未检测到α7-KO的变化。骨基质合成。由于M3R-KO的骨骼结构类似于全身性病变的骨骼,因此使用激动剂给予M3R建立新的治疗策略以改善骨骼质量可能很有价值。

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