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循环缺氧与机械刺激对人骨髓间充质干细胞分化的联合作用:一种治疗骨质流失的新方法。

Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.

作者信息

Camacho-Cardenosa Marta, Pulido-Escribano Victoria, Torrecillas-Baena Bárbara, Quesada-Gómez Jose Manuel, Herrera-Martínez Aura D, Sola-Guirado Rafael R, Dorado Gabriel, Gálvez-Moreno María Ángeles, Casado-Díaz Antonio

机构信息

Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.

Department Mecánica, Escuela Politécnica Superior, Universidad de Córdoba, 14071 Córdoba, Spain.

出版信息

J Clin Med. 2024 Sep 28;13(19):5805. doi: 10.3390/jcm13195805.

DOI:10.3390/jcm13195805
PMID:39407866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11476683/
Abstract

The prevention and treatment of bone loss and osteoporotic fractures is a public health challenge. Combined with normobaric hypoxia, whole-body vibration has a high clinic potential in bone health and body composition. The effect of this therapy may be mediated by its action on bone marrow mesenchymal stem cells (MSCs). Evaluate the effects of cyclic low-vibration stimuli and/or hypoxia on bone marrow-derived human MSC differentiation. MSCs were exposed four days per week, two hours/day, to hypoxia (3% O) and/or vibration before they were induced to differentiate or during differentiation into osteoblasts or adipocytes. Gene and protein expression of osteoblastic, adipogenic, and cytoskeletal markers were studied, as well as extracellular matrix mineralization and lipid accumulation. early osteoblastic markers increased in undifferentiated MSCs, pretreated in hypoxia and vibration. This pretreatment also increased mRNA levels of osteoblastic genes and beta-catenin protein in the early stages of differentiation into osteoblasts without increasing mineralization. When MSCs were exposed to vibration under hypoxia or normoxia during osteoblastic differentiation, mineralization increased with respect to cultures without vibrational stimuli. In MSCs differentiated into adipocytes, both in those pretreated as well as exposed to different conditions during differentiation, lipid formation decreased. Changes in adipogenic gene expression and increased beta-catenin protein were observed in cultures treated during differentiation. Exposure to cyclic hypoxia in combination with low-intensity vibratory stimuli had positive effects on osteoblastic differentiation and negative ones on adipogenesis of bone marrow-derived MSCs. These results suggest that in elderly or frail people with difficulty performing physical activity, exposure to normobaric cyclic hypoxia and low-density vibratory stimuli could improve bone metabolism and health.

摘要

骨量减少和骨质疏松性骨折的预防与治疗是一项公共卫生挑战。与常压性缺氧相结合,全身振动在骨骼健康和身体成分方面具有很高的临床潜力。这种疗法的效果可能是通过其对骨髓间充质干细胞(MSC)的作用来介导的。评估周期性低振动刺激和/或缺氧对人骨髓来源的MSC分化的影响。在诱导MSC分化为成骨细胞或脂肪细胞之前或分化过程中,每周四天,每天两小时将MSC暴露于缺氧(3%氧气)和/或振动环境中。研究了成骨、脂肪生成和细胞骨架标志物的基因和蛋白表达,以及细胞外基质矿化和脂质积累情况。在缺氧和振动预处理的未分化MSC中,早期成骨标志物增加。这种预处理还增加了分化为成骨细胞早期阶段的成骨基因mRNA水平和β-连环蛋白蛋白水平,但没有增加矿化。当成骨细胞分化过程中,MSC在缺氧或常氧条件下暴露于振动时,与无振动刺激的培养物相比,矿化增加。在分化为脂肪细胞的MSC中,无论是预处理的还是在分化过程中暴露于不同条件下的,脂质形成均减少。在分化过程中处理的培养物中观察到脂肪生成基因表达的变化和β-连环蛋白蛋白的增加。暴露于周期性缺氧与低强度振动刺激相结合对骨髓来源的MSC的成骨细胞分化有积极影响,对脂肪生成有消极影响。这些结果表明,对于难以进行体育活动的老年人或体弱者,暴露于常压性周期性缺氧和低密度振动刺激可能会改善骨代谢和骨骼健康。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9258/11476683/ed1a76da8b35/jcm-13-05805-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9258/11476683/c4ea65b87701/jcm-13-05805-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9258/11476683/ed1a76da8b35/jcm-13-05805-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9258/11476683/b52c25650b13/jcm-13-05805-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9258/11476683/47c8f9579d81/jcm-13-05805-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9258/11476683/ed1a76da8b35/jcm-13-05805-g010.jpg

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Effects of intermittent hypoxia and whole-body vibration training on health-related outcomes in older adults.间歇性低氧和全身振动训练对老年人健康相关结局的影响。
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Front Endocrinol (Lausanne). 2023 May 9;14:1035186. doi: 10.3389/fendo.2023.1035186. eCollection 2023.
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Glucose transporters GLUT1, GLUT3, and GLUT4 have different effects on osteoblast proliferation and metabolism.葡萄糖转运蛋白GLUT1、GLUT3和GLUT4对成骨细胞的增殖和代谢有不同影响。
Front Physiol. 2022 Nov 29;13:1035516. doi: 10.3389/fphys.2022.1035516. eCollection 2022.
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Resistance circuit training combined with hypoxia stimulates bone system of older adults: A randomized trial.抗阻训练联合低氧刺激老年人骨系统:一项随机试验。
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