缺氧条件下牙髓源性间充质干细胞外泌体对骨关节炎软骨细胞的影响。

IF 2.1 4区 医学 Q3 CELL BIOLOGY
Habip Karaturk, Zeynep Burcin Gonen, Recep Saraymen, Nur Seda Gokdemir, Hasan Salkin
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引用次数: 0

摘要

目的:骨关节炎是世界范围内致残的常见原因。外泌体是细胞外囊泡,可发挥旁分泌和内分泌作用。DPSCs外泌体为阐明与细胞增殖、分化和免疫调节相关的各种功能提供了新的研究途径。我们假设在缺氧诱导的培养条件下产生的DPSC外泌体可能对骨关节炎软骨细胞具有抗炎作用,并可能重新调节骨关节炎中增加的炎症反应。我们还假设,缺氧条件下产生的DPSC外泌体可能会再次诱导骨关节炎中糖胺聚糖生成的减少。材料和方法:分别在缺氧(3% O2)和常氧(21% O2)条件下从DPSCs中分离外泌体,并应用于OA软骨细胞。通过定量、形态学和分析四联蛋白标记物来表征外泌体。外泌体处理OA软骨细胞48小时后,进行细胞增殖、凋亡、活力、糖胺聚糖试验和炎症细胞因子分析。结果:我们的研究结果显示,缺氧条件下产生的DPSC外泌体明显抑制骨关节炎软骨细胞的促炎细胞因子(p p)。结论:考虑到OA与炎症成分相关,缺氧条件下产生的DPSC外泌体阻止骨关节炎软骨细胞中促炎细胞因子的形成,对骨关节炎软骨细胞具有治疗作用。我们的研究首次证明缺氧条件下dpsc来源的外泌体对骨关节炎软骨细胞的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of dental pulp-derived mesenchymal stem cell exosomes produced under hypoxia conditions on osteoarthritic chondrocytes.

Purpose: Osteoarthritis is a common cause of disability worldwide. Exosomes are extracellular vesicles and can exert paracrine and endocrine actions. DPSCs exosomes offer a new avenue of research that may elucidate various functions related to cell proliferation, differentiation, and immunomodulation. We hypothesized that DPSC exosomes produced under hypoxia-induced culture conditions may have an anti-inflammatory effect on osteoarthritic chondrocytes and may re-regulate the inflammatory response that is increased in osteoarthritis. We also hypothesized that the decreased glycosaminoglycan production in osteoarthritis may be re-induced by DPSC exosomes produced under hypoxia.

Materials and methods: Exosomes were isolated from DPSCs under hypoxic (3% O2) and normoxic conditions (21% O2) separately and were applied to OA chondrocyte cells. Quantification, morphology and analysis of tetraspanin markers were performed to characterize the exosomes. After the OA chondrocytes were treated with exosomes for 48 hours, they were prepared for cell proliferation, apoptosis, viability, glycosaminoglycan tests, and inflammatory cytokine analysis.

Results: Our results show that the pro-inflammatory cytokines were significantly suppressed in osteoarthritic chondrocytes by DPSC exosomes produced under hypoxia (p < 0.05). Exosomes of DPSCs grown in a hypoxia environment dramatically increase the amount of GAG in OA chondrocytes, giving clues that they can be used in cartilage regeneration (p < 0.001).

Conclusion: Considering that OA is associated with inflammatory components, DPSC exosome produced under hypoxic conditions prevents the formation of proinflammatory cytokines in osteoarthritic chondrocytes and shows therapeutic effects on osteoarthritic chondrocytes. Our study provides the first evidence showing the efficacy of DPSC-derived exosomes produced under hypoxia on osteoarthritic chondrocytes.

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来源期刊
Connective Tissue Research
Connective Tissue Research 生物-细胞生物学
CiteScore
6.60
自引率
3.40%
发文量
37
审稿时长
2 months
期刊介绍: The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.
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