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缺氧诱导因子-1α 在周期性牵张诱导骨髓间充质干细胞成骨分化中的表达。

Expression of HIF‑1α in cycling stretch‑induced osteogenic differentiation of bone mesenchymal stem cells.

机构信息

Department of Stomatology, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266011, P.R. China.

Department of Orthodontics II, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266011, P.R. China.

出版信息

Mol Med Rep. 2019 Nov;20(5):4489-4498. doi: 10.3892/mmr.2019.10715. Epub 2019 Sep 30.

Abstract

During orthodontic treatment, mechanical force is applied to the teeth, and following a series of complex metabolism changes, the position of the teeth in the alveolar bone change. This process is closely associated with primitive bone mesenchymal stem cells (BMSCs), which may differentiate into osteoblasts precursor cell. A hypoxic microenvironment may be caused by orthodontic mechanical forces between the alveolar bone and the root. Hypoxia‑inducible factor 1α (HIF‑1α) is a specific receptor that adapts to a hypoxic environment. The present study was designed to investigate whether HIF‑1α was involved in the osteoblastic differentiation of BMSCs induced by cyclic tensile stress. During this process, HIF‑1α mRNA and protein expression were detected using a reverse transcription‑quantitative polymerase chain reaction and western blotting. It was revealed that alkaline phosphatase activity increased in a time‑dependent manner in three different stretching strength groups, which indicates that cyclic stretch promotes the osteogenic differentiation of BMSCs. The optimal force stage of osteogenesis was an unexpected discovery, which will provide theoretical guidance for selecting the most suitable orthodontic force for tooth movement in clinical orthodontic treatment. Most importantly, all experiments revealed that HIF‑1α mRNA and protein were significantly increased following stretching treatment in BMSCs. It was therefore concluded that HIF‑1α may be involved in BMSCs modulating osteogenic metabolism during exposure to cyclic stretch and a hypoxic microenvironment, which may prove useful for the reconstruction of a jaw during orthodontic treatment.

摘要

在正畸治疗过程中,机械力施加于牙齿,随后一系列复杂的代谢变化会导致牙齿在牙槽骨中的位置发生改变。这个过程与原始骨间充质干细胞(BMSCs)密切相关,后者可能分化为成骨细胞前体细胞。正畸机械力可能会在牙槽骨和牙根之间引起缺氧微环境。缺氧诱导因子 1α(HIF-1α)是一种适应缺氧环境的特定受体。本研究旨在探讨 HIF-1α 是否参与周期性张应变诱导的 BMSCs 成骨分化。在这个过程中,使用逆转录-定量聚合酶链反应和蛋白质印迹法检测 HIF-1α mRNA 和蛋白表达。结果表明,在三个不同拉伸强度组中,碱性磷酸酶活性呈时间依赖性增加,这表明周期性拉伸促进 BMSCs 的成骨分化。成骨的最佳力阶段是一个意外的发现,这将为临床正畸治疗中选择最适合牙齿移动的正畸力提供理论指导。最重要的是,所有实验均表明,BMSCs 经拉伸处理后 HIF-1α mRNA 和蛋白表达显著增加。因此,可以得出结论,HIF-1α 可能参与 BMSCs 调节周期性拉伸和缺氧微环境下的成骨代谢,这可能对正畸治疗中颌骨重建有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ed/6797986/ffe52c43a406/MMR-20-05-4489-g00.jpg

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