Department of Biochemistry, University of Missouri, Columbia, MO 65211, United States of America.
Department of Child Health, University of Missouri, Columbia, MO 65211, United States of America.
Mol Genet Metab. 2021 Apr;132(4):244-253. doi: 10.1016/j.ymgme.2021.02.004. Epub 2021 Feb 20.
Osteogenesis imperfecta (OI) is a heritable connective tissue disorder with patients exhibiting bone fragility and muscle weakness. The synergistic biochemical and biomechanical relationship between bone and muscle is a critical potential therapeutic target, such that muscle weakness should not be ignored. Previous studies demonstrated mitochondrial dysfunction in the skeletal muscle of oim/oim mice, which model a severe human type III OI. Here, we further characterize this mitochondrial dysfunction and evaluate several parameters of whole body and skeletal muscle metabolism. We demonstrate reduced mitochondrial respiration in female gastrocnemius muscle, but not in liver or heart mitochondria, suggesting that mitochondrial dysfunction is not global in the oim/oim mouse. Myosin heavy chain fiber type distributions were altered in the oim/oim soleus muscle with a decrease (-33 to 50%) in type I myofibers and an increase (+31%) in type IIa myofibers relative to their wildtype (WT) littermates. Additionally, altered body composition and increased energy expenditure were observed oim/oim mice relative to WT littermates. These results suggest that skeletal muscle mitochondrial dysfunction is linked to whole body metabolic alterations and to skeletal muscle weakness in the oim/oim mouse.
成骨不全症（OI）是一种遗传性结缔组织疾病，患者表现为骨骼脆弱和肌肉无力。骨骼和肌肉之间协同的生化和生物力学关系是一个关键的潜在治疗靶点，因此不应忽视肌肉无力的问题。先前的研究表明，oim/oim 小鼠（一种严重的 III 型成骨不全症的人类模型）的骨骼肌存在线粒体功能障碍。在这里，我们进一步描述了这种线粒体功能障碍，并评估了全身和骨骼肌代谢的几个参数。我们发现雌性比目鱼肌的线粒体呼吸功能降低，但肝脏和心脏的线粒体没有降低，这表明 oim/oim 小鼠的线粒体功能障碍不是全身性的。oim/oim 比目鱼肌的肌球蛋白重链纤维类型分布发生改变，I 型肌纤维减少（-33%至 50%），IIa 型肌纤维增加（+31%），与野生型（WT）同窝仔鼠相比。此外，与 WT 同窝仔鼠相比，oim/oim 小鼠的身体成分发生改变，能量消耗增加。这些结果表明，骨骼肌线粒体功能障碍与全身代谢改变以及 oim/oim 小鼠的骨骼肌无力有关。
