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成骨分化的人脂肪组织和骨髓基质细胞的比较蛋白质组学分析。

Comparative proteomic analysis of osteogenic differentiated human adipose tissue and bone marrow-derived stromal cells.

机构信息

Department of Plastic Surgery, BG University Hospital Bergmannsheil, Bochum, Germany.

Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.

出版信息

J Cell Mol Med. 2020 Oct;24(20):11814-11827. doi: 10.1111/jcmm.15797. Epub 2020 Sep 3.

Abstract

Mesenchymal stromal cells are promising candidates for regenerative applications upon treatment of bone defects. Bone marrow-derived stromal cells (BMSCs) are limited by yield and donor morbidity but show superior osteogenic capacity compared to adipose-derived stromal cells (ASCs), which are highly abundant and easy to harvest. The underlying reasons for this difference on a proteomic level have not been studied yet. Human ASCs and BMSCs were characterized by FACS analysis and tri-lineage differentiation, followed by an intraindividual comparative proteomic analysis upon osteogenic differentiation. Results of the proteomic analysis were followed by functional pathway analysis. 29 patients were included with a total of 58 specimen analysed. In these, out of 5148 identified proteins 2095 could be quantified in >80% of samples of both cell types, 427 in >80% of ASCs only and 102 in >80% of BMSCs only. 281 proteins were differentially regulated with a fold change of >1.5 of which 204 were higher abundant in BMSCs and 77 in ASCs. Integrin cell surface interactions were the most overrepresented pathway with 5 integrins being among the proteins with highest fold change. Integrin 11a, a known key protein for osteogenesis, could be identified as strongly up-regulated in BMSC confirmed by Western blotting. The integrin expression profile is one of the key distinctive features of osteogenic differentiated BMSCs and ASCs. Thus, they represent a promising target for modifications of ASCs aiming to improve their osteogenic capacity and approximate them to that of BMSCs.

摘要

间充质基质细胞是治疗骨缺损后再生应用的有前途的候选者。骨髓基质细胞 (BMSCs) 的产量有限,且供体发病率高,但与脂肪基质细胞 (ASCs) 相比,具有更好的成骨能力,ASCs 含量丰富且易于采集。在蛋白质组学水平上,这种差异的根本原因尚未得到研究。通过 FACS 分析和三系分化对人 ASC 和 BMSC 进行了表征,然后对成骨分化后的个体进行了比较蛋白质组学分析。蛋白质组学分析的结果随后进行了功能途径分析。共纳入 29 例患者,共分析了 58 例标本。在这些标本中,在 5148 种鉴定蛋白中,有 2095 种在两种细胞类型的>80%样本中可定量,427 种仅在 ASC 中>80%的样本中可定量,102 种仅在 BMSC 中>80%的样本中可定量。有 281 种蛋白质的调节倍数>1.5,其中 204 种在 BMSC 中丰度更高,77 种在 ASC 中丰度更高。细胞表面整合素相互作用是最具代表性的途径,其中 5 种整合素是折叠变化最大的蛋白质之一。整合素 11a 是成骨的已知关键蛋白,通过 Western blot 证实其在 BMSC 中被强烈上调。整合素表达谱是成骨分化的 BMSC 和 ASC 的关键特征之一。因此,它们代表了一种有前途的靶点,可以对 ASCs 进行修饰,旨在提高其成骨能力并使其接近 BMSCs。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3620/7579700/ee4dff937297/JCMM-24-11814-g001.jpg

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