Stadelmann Vincent A, Brun Julia, Bonnet Nicolas
AO Research Institute Davos , Davos-Platz, Switzerland.
Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine , Geneva, Switzerland.
Bonekey Rep. 2015 Dec 23;4:768. doi: 10.1038/bonekey.2015.138. eCollection 2015.
The aim of this laboratory method is to describe two approaches for the investigation of bone responses to mechanical loading in mice in vivo. The first is running exercise, because it is easily translatable clinically, and the second is axial compression of the tibia, because it is precisely controllable. The effects of running exercise, and in general physical activity, on bone tissue have been shown to be both direct through mechanical loading (ground impact and muscle tension) and indirect through metabolic changes. Therefore, running exercise has been considered the most convenient preclinical model for demonstrating the general idea that exercise is good for bone health, either early in age for increasing peak bone mass or later in age by slowing down bone loss. However, numerous combinations of protocols have been reported, which makes it difficult to formulate a simple take-home message. This laboratory method also provides a detailed description of in vivo direct mechanical axial compression of the mouse tibia. The effects of mechanical loading depend on the force (strain), frequency, waveform and duration of application, and they range from bone anabolism with low bone remodeling, inducing lamellar bone accumulation, to bone catabolism with high bone remodeling, leading to microdamage, woven bone formation and bone loss. Direct in vivo loading models are extensively used to study mechanotransduction pathways, and contribute by this way to the development of new bone anabolism treatments. Although it is particularly difficult to assemble an internationally adopted protocol description, which would give reproducible bone responses, here we have attempted to provide a comprehensive guide for best practice in performing running exercise and direct in vivo mechanical loading in the laboratory.
本实验方法的目的是描述两种在小鼠体内研究骨骼对机械负荷反应的方法。第一种是跑步运动，因为它在临床上易于转化应用；第二种是胫骨轴向压缩，因为它可以精确控制。跑步运动以及一般的体育活动对骨组织的影响已被证明既有通过机械负荷产生的直接影响（地面冲击和肌肉张力），也有通过代谢变化产生的间接影响。因此，跑步运动被认为是最方便的临床前模型，用于证明运动有益于骨骼健康这一普遍观点，即在年轻时可增加骨峰值，在年老时可减缓骨质流失。然而，已经报道了众多不同的实验方案组合，这使得难以形成一个简单明了的结论。本实验方法还详细描述了小鼠胫骨的体内直接机械轴向压缩。机械负荷的影响取决于力（应变）、频率、波形和施加持续时间，其范围从低骨重塑的骨合成代谢（诱导板层骨积累）到高骨重塑的骨分解代谢（导致微损伤、编织骨形成和骨质流失）。体内直接负荷模型被广泛用于研究机械转导途径，并以此促进新的骨合成代谢治疗方法的开发。尽管特别难以汇编一个能产生可重复骨骼反应的国际通用方案描述，但在此我们试图提供一份在实验室中进行跑步运动和体内直接机械负荷的最佳实践综合指南。
