Direct effects of mitochondrial dysfunction on poor bone health in Leigh syndrome
Direct effects of mitochondrial dysfunction on poor bone health in Leigh syndrome
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DOI：
10.1016/j.bbrc.2017.09.045
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发表时间：
2017-11-04
影响因子：
3.1
通讯作者：
Nonaka, Kazuaki
中科院分区：
文献类型：
--
作者：
Kato, Hiroki;Han, Xu;Nonaka, Kazuaki
线粒体疾病是由核或线粒体DNA突变引起的线粒体功能异常的结果。骨骼健康状况不佳最近被认为是线粒体疾病的症状;然而，线粒体功能下降和线粒体疾病中骨骼健康状况不佳之间的直接联系尚未得到证实。在这项研究中，从Leigh综合征（LS）（一种线粒体疾病）儿童中分离出人类脱落乳牙（SHED）干细胞，并分析了线粒体功能下降对骨骼健康状况不良的影响。与对照SHED相比，LS SHED显示成骨细胞分化和钙矿化减少。LS SHED组细胞内和线粒体内钙离子浓度均低于对照组。此外，与对照组相比，LS SHED的线粒体活性降低，无论是否有成骨细胞分化。我们的研究结果表明，降低成骨细胞分化潜力和成骨细胞功能有助于线粒体疾病的骨健康状况差。(C)2017爱思唯尔公司All rights reserved.
Mitochondrial diseases are the result of aberrant mitochondrial function caused by mutations in either nuclear or mitochondrial DNA. Poor bone health has recently been suggested as a symptom of mitochondrial diseases; however, a direct link between decreased mitochondrial function and poor bone health in mitochondrial disease has not been demonstrated. In this study, stem cells from human exfoliated deciduous teeth (SHED) were isolated from a child with Leigh syndrome (LS), a mitochondrial disease, and the effects of decreased mitochondrial function on poor bone health were analyzed. Compared with control SHED, LS SHED displayed decreased osteoblastic differentiation and calcium mineralization. The intracellular and mitochondrial calcium levels were lower in LS SHED than in control SHED. Furthermore, the mitochondrial activity of LS SHED was decreased compared with control SHED both with and without osteoblastic differentiation. Our results indicate that decreased osteoblast differentiation potential and osteoblast function contribute to poor bone health in mitochondrial diseases. (C) 2017 Elsevier Inc. All rights reserved.