Laboratory for Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany.
Life Sci. 2012 Nov 27;91(21-22):997-1002. doi: 10.1016/j.lfs.2012.07.024. Epub 2012 Jul 31.
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.
在成纤维细胞上刺激烟碱型和毒蕈碱型乙酰胆碱受体（nAChR 和 mAChR）后，观察到肺中的胶原蛋白合成增加。由于胶原蛋白合成是骨折愈合和骨重塑过程中的一个重要过程，我们想知道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 nAChRα7（α7-KO）和 mAChR M3R（M3R-KO）雄性基因敲除小鼠与其相应野生型（WT）的相关性。使用 3D 微 CT 分析右侧股骨、Th13 和 L1 椎体、左侧股骨进行三点弯曲试验和肱骨进行实时 RT-PCR 分析。
与 WT 相比，M3R-KO 的相对骨体积、骨小梁厚度、骨小梁数量、骨表面密度显著降低，骨小梁分离和结构模型指数显著增加。与 WT 相比，M3R-KO 的弯曲刚度显著降低，并且胶原蛋白 1α1 和 1α2 mRNA 表达下调。使用微 CT、生物力学测试和胶原 mRNA 表达，未检测到α7-KO 的变化。
我们的结果表明，nAChRα7 不参与骨胶原蛋白合成的调节，而 M3R 对松质骨微结构、弯曲刚度和骨基质合成有刺激作用。由于 M3R-KO 表现出与系统性疾病骨骼相似的骨骼结构，因此使用 M3R 激动剂进行治疗可能是一种有价值的策略，以改善骨骼质量。
