Effect of Brain-Derived Neurotrophic Factor on the Neurogenesis and Osteogenesis in Bone Engineering
Effect of Brain-Derived Neurotrophic Factor on the Neurogenesis and Osteogenesis in Bone Engineering
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脑源性神经营养因子对骨工程神经发生和成骨的影响
DOI：
10.1089/ten.tea.2017.0462
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发表时间：
2018-04-10
影响因子：
4.1
通讯作者：
Kang, Yunqing
中科院分区：
文献类型：
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作者：
Liu, Qing;Lei, Lei;Kang, Yunqing
在骨生长过程中，再生区域缺乏神经化血管网络会影响随后的骨质量。本研究旨在探讨脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）是否能促进人骨髓间充质干细胞（human bone mesenchymal stem cells，hBMSCs）的神经发生和成骨，以促进组织工程中骨的形成。最初，确定了促进hBMSC体外增殖的安全有效的BDNF浓度。随后，检查矿化结节形成和碱性磷酸酶（ALP）活性和ALP基因表达的评估显示，BDNF在hBMSCs中引起反应的最有效浓度为100 ng/mL。此外，我们发现通过与TrkB受体结合，下游Erk 1/2被磷酸化，从而促进与成骨细胞分化相关的转录因子如Runx 2和Osterix的表达。我们还发现，到治疗后第7天，神经源性生物标志物p75和s100在100 ng/mL BDNF治疗的hBMSCs中高度表达。最后，BDNF对新形成的组织中的骨发生和神经发生的影响使用具有α-磷酸三钙支架的动物模型进行评估。这表明，用100 ng/mL BDNF治疗促进hBMSCs在体内的成骨和神经发生，通过增加成骨标志物骨钙素和各种神经生物标志物的表达，包括微管相关蛋白2，胶质细胞酸性蛋白，神经/胶质细胞抗原2和微管蛋白III。这项研究表明，BDNF促进hBMSC在体外和体内的成骨和神经发生，BDNF可能通过增加神经发生间接促进成骨。这进一步表明，在骨工程过程中鼓励中和将导致骨缺损的有效修复。这项研究也可能为相关领域提供见解，如骨感知和牙种植后的应力反馈调节。
During bone growth, the lack of a neuralized vascular network in the regenerating area can affect subsequent bone quality. This study aimed to investigate if brain-derived neurotrophic factor (BDNF) could promote neurogenesis and osteogenesis in human bone mesenchymal stem cells (hBMSCs) to improve bone formation during tissue engineering. Initially, a safe and effective BDNF concentration that facilitated hBMSC proliferation in vitro was determined. Subsequently, examination of mineralized nodule formation and evaluation of alkaline phosphatase (ALP) activity and ALP gene expression revealed that the most effective concentration of BDNF to elicit a response in hBMSCs was 100ng/mL. In addition, we found out that by binding with TrkB receptor, the downstream Erk1/2 was phosphorylated, which promoted the expression of transcription factors, such as Runx2 and Osterix that are associated with osteoblast differentiation. We also found that by day 7 post-treatment, the neurogenic biomarkers, p75 and s100, were highly expressed in 100ng/mL BDNF-treated hBMSCs. Finally, the effects of BDNF on osteogenesis and neurogenesis in newly formed tissues were assessed using animal models with a -tricalcium phosphate scaffold. This revealed that treatment with 100ng/mL BDNF promoted the osteogenesis and neurogenesis of hBMSCs in vivo by increasing expression of the osteogenic marker osteocalcin and various neurogenic biomarkers, including microtubule-associated protein 2, glial fibrillary acidic protein, neural/glial antigen 2, and -tubulin III. This study has demonstrated that BDNF promotes hBMSC osteogenesis and neurogenesis in vitro and in vivo, and that BDNF may indirectly promote osteogenesis through increased neurogenesis. This further suggests that encouraging neutralization during bone engineering will lead to effective repairing of bone defects. The study may also provide insight into related fields, such as osseoperception and stress feedback regulation after dental implantation.