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p75NTR 通过上调 α1 整合素表达来优化人牙周膜干细胞的成骨潜能。

p75NTR optimizes the osteogenic potential of human periodontal ligament stem cells by up-regulating α1 integrin expression.

机构信息

Department of Stomatology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Hospital of Stomatology, Zunyi Medical University, Zunyi, China.

出版信息

J Cell Mol Med. 2020 Jul;24(13):7563-7575. doi: 10.1111/jcmm.15390. Epub 2020 May 18.


DOI:10.1111/jcmm.15390
PMID:32424966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7339167/
Abstract

Human periodontal ligament stem cells (hPDLSCs) are a promising source in regenerative medicine. Due to the complexity and heterogeneity of hPDLSCs, it is critical to isolate homogeneous hPDLSCs with high regenerative potential. In this study, p75 neurotrophin receptor (p75NTR) was used to isolate p75NTR and p75NTR hPDLSCs by fluorescence-activated cell sorting. Differences in osteogenic differentiation among p75NTR , p75NTR and unsorted hPDLSCs were observed. Differential gene expression profiles between p75NTR and p75NTR hPDLSCs were analysed by RNA sequencing. α1 Integrin (ITGA1) small interfering RNA and ITGA1-overexpressing adenovirus were used to transfect p75NTR and p75NTR hPDLSCs. The results showed that p75NTR hPDLSCs demonstrated superior osteogenic capacity than p75NTR and unsorted hPDLSCs. Differentially expressed genes between p75NTR and p75NTR hPDLSCs were highly involved in the extracellular matrix-receptor interaction signalling pathway, and p75NTR hPDLSCs expressed higher ITGA1 levels than p75NTR hPDLSCs. ITGA1 silencing inhibited the osteogenic differentiation of p75NTR hPDLSCs, while ITGA1 overexpression enhanced the osteogenic differentiation of p75NTR hPDLSCs. These findings indicate that p75NTR optimizes the osteogenic potential of hPDLSCs by up-regulating ITGA1 expression, suggesting that p75NTR can be used as a novel cell surface marker to identify and purify hPDLSCs to promote their applications in regenerative medicine.

摘要

人牙周韧带干细胞(hPDLSCs)是再生医学中有前途的来源。由于 hPDLSCs 的复杂性和异质性,分离具有高再生潜能的同质 hPDLSCs 至关重要。在这项研究中,使用 p75 神经生长因子受体(p75NTR)通过荧光激活细胞分选分离 p75NTR 和 p75NTR hPDLSCs。观察了 p75NTR、p75NTR 和未分选的 hPDLSCs 之间成骨分化的差异。通过 RNA 测序分析了 p75NTR 和 p75NTR hPDLSCs 之间的差异基因表达谱。使用 α1 整合素(ITGA1)小干扰 RNA 和 ITGA1 过表达腺病毒转染 p75NTR 和 p75NTR hPDLSCs。结果表明,p75NTR hPDLSCs 表现出比 p75NTR 和未分选的 hPDLSCs 更高的成骨能力。p75NTR 和 p75NTR hPDLSCs 之间差异表达的基因高度参与细胞外基质-受体相互作用信号通路,并且 p75NTR hPDLSCs 表达的 ITGA1 水平高于 p75NTR hPDLSCs。ITGA1 沉默抑制了 p75NTR hPDLSCs 的成骨分化,而 ITGA1 过表达增强了 p75NTR hPDLSCs 的成骨分化。这些发现表明,p75NTR 通过上调 ITGA1 表达来优化 hPDLSCs 的成骨潜能,表明 p75NTR 可用作鉴定和纯化 hPDLSCs 的新型细胞表面标志物,以促进其在再生医学中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/0018821e3bfd/JCMM-24-7563-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/6ae8db2200cb/JCMM-24-7563-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/7ed9de341b38/JCMM-24-7563-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/edab4837034d/JCMM-24-7563-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/e98d2c8f5e10/JCMM-24-7563-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/d8869d381bd8/JCMM-24-7563-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/886929f5bf77/JCMM-24-7563-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/0018821e3bfd/JCMM-24-7563-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/6ae8db2200cb/JCMM-24-7563-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/7ed9de341b38/JCMM-24-7563-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/edab4837034d/JCMM-24-7563-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/e98d2c8f5e10/JCMM-24-7563-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/d8869d381bd8/JCMM-24-7563-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/886929f5bf77/JCMM-24-7563-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/7339167/0018821e3bfd/JCMM-24-7563-g007.jpg

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[4]
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[5]
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