Skeletal muscle specific mitochondrial dysfunction and altered energy metabolism in a murine model (oim/oim) of severe osteogenesis imperfecta.
Skeletal muscle specific mitochondrial dysfunction and altered energy metabolism in a murine model (oim/oim) of severe osteogenesis imperfecta.
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DOI：
10.1016/j.ymgme.2021.02.004
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发表时间：
2021-04
影响因子：
3.8
通讯作者：
Phillips CL
中科院分区：
文献类型：
--
作者：
Gremminger VL;Harrelson EN;Crawford TK;Ohler A;Schulz LC;Rector RS;Phillips CL
成骨不全(OI)是一种遗传性结缔组织疾病，患者表现为骨脆性和肌肉无力。骨骼和肌肉之间的协同生化和生物力学关系是一个重要的潜在治疗靶点，因此肌肉无力是不容忽视的。先前的研究表明，OIM/OIM小鼠骨骼肌线粒体功能障碍，这是一种严重的人类III型OI模型。在这里，我们进一步描述这种线粒体功能障碍，并评估全身和骨骼肌代谢的几个参数。我们发现雌性腓肠肌的线粒体呼吸减少，但在肝脏或心脏线粒体中没有，这表明线粒体功能障碍在OIM/OIM小鼠中并不是全球性的。OIM/OIM比目鱼肌的肌球蛋白重链纤维类型分布发生了改变，与野生型(WT)相比，I型肌纤维减少(-33%~50%)，IIa型肌纤维增加(+31%)。此外，与WT仔鼠相比，OIM/OIM小鼠的身体成分发生了变化，能量消耗增加。这些结果表明，在OIM/OIM小鼠中，骨骼肌线粒体功能障碍与全身代谢变化和骨骼肌无力有关。
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.
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影响因子：
16.2
作者：
Mahendran Y;Cederberg H;Vangipurapu J;Kangas AJ;Soininen P;Kuusisto J;Uusitupa M;Ala-Korpela M;Laakso M
通讯作者：
Laakso M
影响因子：
6.2
作者：
Folkestad, Lars;Hald, Jannie Dahl;Brixen, Kim
通讯作者：
Brixen, Kim
影响因子：
5.5
作者：
Benard, G.;Faustin, B.;Rossignol, R.
通讯作者：
Rossignol, R.
哺乳动物线粒体蛋白质组的组织异质性
影响因子：
5.5
作者：
Johnson, D. Thor;Harris, Robert A.;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
DOI：
10.1016/j.matbio.2018.03.010
发表时间：
2018-10
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Morello R
通讯作者：
Morello R