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Comparative proteomic analysis of osteogenic differentiated human adipose tissue and bone marrow-derived stromal cells.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-09-03 , DOI: 10.1111/jcmm.15797
Mehran Dadras 1 , Caroline May 2 , Johannes Maximilian Wagner 1 , Christoph Wallner 1 , Mustafa Becerikli 1 , Stephanie Dittfeld 1 , Bettina Serschnitzki 2 , Lukas Schilde 2 , Annika Guntermann 2 , Christina Sengstock 3 , Manfred Köller 3 , Dominik Seybold 3 , Jan Geßmann 3 , Thomas Armin Schildhauer 3 , Marcus Lehnhardt 1 , Katrin Marcus 2 , Björn Behr 1
Affiliation  

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.

中文翻译:

成骨分化的人脂肪组织和骨髓来源的基质细胞的比较蛋白质组学分析。

间充质基质细胞有望在治疗骨缺损时用于再生应用。骨髓基质细胞(BMSC)受产量和供体发病率的限制,但与脂肪来源的基质细胞(ASC)相比,成骨能力强,后者高度丰富且易于收获。尚未在蛋白质组学水平上研究这种差异的根本原因。人类ASC和BMSC的特征是通过FACS分析和三系分化,然后在成骨分化时进行个体内比较蛋白质组学分析。蛋白质组学分析的结果之后是功能途径分析。纳入29例患者,共分析58例标本。在这5148种已鉴定的蛋白质中,可以在两种细胞类型的> 80%的样品中对2095种蛋白质进行定量,仅在> 80%的ASC中有427个,在> 80%的BMSC中只有102个。281种蛋白质被差异调节,其倍数变化> 1.5,其中BMSC中204种蛋白质含量较高,而ASC中77种蛋白质含量较高。整联蛋白细胞表面相互作用是最被代表的途径,其中5个整联蛋白是具有最高倍数变化的蛋白质之一。整合素11a是已知的成骨关键蛋白,可以通过Western blot证实其在BMSC中强烈上调。整联蛋白表达谱是成骨分化的BMSC和ASC的关键独特特征之一。因此,它们代表了ASC修饰的有希望的目标,旨在提高其成骨能力并使它们接近于BMSC。281种蛋白质被差异调节,其倍数变化> 1.5,其中BMSC中204种蛋白质含量较高,而ASC中77种蛋白质含量较高。整联蛋白细胞表面相互作用是最被代表的途径,其中5个整联蛋白是具有最高倍数变化的蛋白质之一。整合素11a是已知的成骨关键蛋白,可以通过Western blot证实其在BMSC中强烈上调。整联蛋白表达谱是成骨分化的BMSC和ASC的关键独特特征之一。因此,它们代表了ASC修饰的有希望的目标,旨在提高其成骨能力并使它们接近于BMSC。281种蛋白质被差异调节,其倍数变化> 1.5,其中BMSC中204种蛋白质含量较高,而ASC中77种蛋白质含量较高。整联蛋白细胞表面相互作用是最被代表的途径,其中5个整联蛋白是具有最高倍数变化的蛋白质之一。整合素11a是已知的成骨关键蛋白,可以通过Western blot证实其在BMSC中强烈上调。整联蛋白表达谱是成骨分化的BMSC和ASC的关键独特特征之一。因此,它们代表了ASC修饰的有希望的目标,旨在提高其成骨能力并使它们接近于BMSC。整联蛋白细胞表面相互作用是最被代表的途径,其中5个整联蛋白是具有最高倍数变化的蛋白质之一。整合素11a是已知的成骨关键蛋白,可以通过Western blot证实其在BMSC中强烈上调。整联蛋白表达谱是成骨分化的BMSC和ASC的关键独特特征之一。因此,它们代表了ASC修饰的有希望的目标,旨在提高其成骨能力并使它们接近于BMSC。整联蛋白细胞表面相互作用是最被代表的途径,其中5个整联蛋白是具有最高倍数变化的蛋白质之一。整合素11a是已知的成骨关键蛋白,可以通过Western blot证实其在BMSC中强烈上调。整联蛋白表达谱是成骨分化的BMSC和ASC的关键独特特征之一。因此,它们代表了ASC修饰的有希望的目标,旨在提高其成骨能力并使它们接近于BMSC。
更新日期:2020-10-22
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