Department of Health Sciences, Institute of Research for Food Safety and Health (IRC-FSH), University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy.
Department of Medical and Surgical Science, University Magna Grecia, 88100 Catanzaro, Italy.
Int J Mol Sci. 2023 Feb 13;24(4):3765. doi: 10.3390/ijms24043765.
Skeletal muscle atrophy is a condition characterized by a loss of muscle mass and muscle strength caused by an imbalance between protein synthesis and protein degradation. Muscle atrophy is often associated with a loss of bone mass manifesting as osteoporosis. The aim of this study was to evaluate if chronic constriction injury (CCI) of the sciatic nerve in rats can be a valid model to study muscle atrophy and consequent osteoporosis. Body weight and body composition were assessed weekly. Magnetic resonance imaging (MRI) was performed on day zero before ligation and day 28 before sacrifice. Catabolic markers were assessed via Western blot and Quantitative Real-time PCR. After the sacrifice, a morphological analysis of the gastrocnemius muscle and Micro-Computed Tomography (Micro-CT) on the tibia bone were performed. Rats that underwent CCI had a lower body weight increase on day 28 compared to the naive group of rats ( < 0.001). Increases in lean body mass and fat mass were also significantly lower in the CCI group ( < 0.001). The weight of skeletal muscles was found to be significantly lower in the ipsilateral hindlimb compared to that of contralateral muscles; furthermore, the cross-sectional area of muscle fibers decreased significantly in the ipsilateral gastrocnemius. The CCI of the sciatic nerve induced a statistically significant increase in autophagic and UPS (Ubiquitin Proteasome System) markers and a statistically significant increase in Pax-7 (Paired Box-7) expression. Micro-CT showed a statistically significant decrease in the bone parameters of the ipsilateral tibial bone. Chronic nerve constriction appeared to be a valid model for inducing the condition of muscle atrophy, also causing changes in bone microstructure and leading to osteoporosis. Therefore, sciatic nerve constriction could be a valid approach to study muscle-bone crosstalk and to identify new strategies to prevent osteosarcopenia.
骨骼肌萎缩是一种肌肉质量和肌肉力量丧失的病症，其原因是蛋白质合成与蛋白质降解之间的失衡。肌肉萎缩通常与骨量的减少有关，表现为骨质疏松症。本研究的目的是评估大鼠坐骨神经慢性缩窄性损伤（CCI）是否可以作为研究肌肉萎缩和随之而来的骨质疏松症的有效模型。每周评估体重和身体成分。在结扎前的第 0 天和牺牲前的第 28 天进行磁共振成像（MRI）。通过 Western blot 和定量实时 PCR 评估分解代谢标志物。牺牲后，对腓肠肌进行形态学分析，并对胫骨进行微计算机断层扫描（Micro-CT）。与未损伤组大鼠相比，CCI 组大鼠在第 28 天的体重增加明显较低（<0.001）。在 CCI 组中，瘦体重和脂肪质量的增加也明显较低（<0.001）。与对侧肌肉相比，同侧后肢的骨骼肌重量明显较低；此外，同侧腓肠肌的肌纤维横截面积明显减小。坐骨神经的 CCI 导致自噬和 UPS（泛素蛋白酶体系统）标志物的统计学显著增加，以及 Pax-7（配对盒 7）表达的统计学显著增加。Micro-CT 显示同侧胫骨骨参数出现统计学显著下降。慢性神经缩窄似乎是一种诱导肌肉萎缩的有效模型，还会导致骨微结构的变化，并导致骨质疏松症。因此，坐骨神经缩窄可能是研究肌肉-骨骼串扰和确定预防骨肌减少症新策略的有效方法。
