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抛物线飞行机动期间短期重力改变条件下培养的人软骨细胞的差异基因表达

Differential gene expression of human chondrocytes cultured under short-term altered gravity conditions during parabolic flight maneuvers.

作者信息

Wehland Markus, Aleshcheva Ganna, Schulz Herbert, Saar Katrin, Hübner Norbert, Hemmersbach Ruth, Braun Markus, Ma Xiao, Frett Timo, Warnke Elisabeth, Riwaldt Stefan, Pietsch Jessica, Corydon Thomas Juhl, Infanger Manfred, Grimm Daniela

机构信息

Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke University, 39120, Magdeburg, Germany.

Max-Delbrück-Center for Molecular Medicine, 13092, Berlin, Germany.

出版信息

Cell Commun Signal. 2015 Mar 20;13:18. doi: 10.1186/s12964-015-0095-9.

Abstract

BACKGROUND

Chondrocytes are the main cellular component of articular cartilage. In healthy tissue, they are embedded in a strong but elastic extracelluar matrix providing resistance against mechanical forces and friction for the joints. Osteoarthritic cartilage, however, disrupted by heavy strain, has only very limited potential to heal. One future possibility to replace damaged cartilage might be the scaffold-free growth of chondrocytes in microgravity to form 3D aggregates.

RESULTS

To prepare for this, we have conducted experiments during the 20th DLR parabolic flight campaign, where we fixed the cells after the first (1P) and the 31st parabola (31P). Furthermore, we subjected chondrocytes to isolated vibration and hypergravity conditions. Microarray and quantitative real time PCR analyses revealed that hypergravity regulated genes connected to cartilage integrity (BMP4, MMP3, MMP10, EDN1, WNT5A, BIRC3). Vibration was clearly detrimental to cartilage (upregulated inflammatory IL6 and IL8, downregulated growth factors EGF, VEGF, FGF17). The viability of the cells was not affected by the parabolic flight, but showed a significantly increased expression of anti-apoptotic genes after 31 parabolas. The IL-6 release of chondrocytes cultured under conditions of vibration was not changed, but hypergravity (1.8 g) induced a clear elevation of IL-6 protein in the supernatant compared with corresponding control samples.

CONCLUSION

Taken together, this study provided new insights into the growth behavior of chondrocytes under short-term microgravity.

摘要

背景

软骨细胞是关节软骨的主要细胞成分。在健康组织中,它们嵌入在坚固但有弹性的细胞外基质中,为关节提供抗机械力和摩擦力的能力。然而,受重度劳损破坏的骨关节炎软骨愈合潜力非常有限。未来一种替代受损软骨的可能性可能是在微重力条件下无支架培养软骨细胞以形成三维聚集体。

结果

为此,我们在德国航空航天中心第20次抛物线飞行实验中进行了实验,在第一次抛物线(1P)和第31次抛物线(31P)后固定细胞。此外,我们使软骨细胞处于孤立的振动和超重力条件下。微阵列和定量实时PCR分析表明,超重力调节与软骨完整性相关的基因(骨形态发生蛋白4、基质金属蛋白酶3、基质金属蛋白酶10、内皮素1、Wnt5a、杆状病毒IAP重复序列包含蛋白3)。振动对软骨明显有害(上调炎症因子白细胞介素6和白细胞介素8,下调生长因子表皮生长因子、血管内皮生长因子、成纤维细胞生长因子17)。细胞活力不受抛物线飞行影响,但在31次抛物线后抗凋亡基因表达显著增加。在振动条件下培养的软骨细胞白细胞介素-6释放没有变化,但与相应对照样品相比,超重力(1.8g)导致上清液中白细胞介素-6蛋白明显升高。

结论

综上所述,本研究为软骨细胞在短期微重力下的生长行为提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e75/4369370/d78d496c2079/12964_2015_95_Fig1_HTML.jpg

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