IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Amirah Zulkifli, Peggy Kong, Shaliny Hrk, Nor Faissal Yasin, Hui Yin Nam, Tunku Kamarul
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引用次数: 0

摘要

由于肌腱的内在修复能力较差,肌腱损伤仍是治疗难题。据推测,通过激活缺氧诱导因子-1α(HIF-1α)对间充质干细胞(MSC)进行缺氧调理,可促进细胞增殖和成腱分化,从而增强肌腱修复过程。为了证明这一点,研究人员对脂肪来源间充质基质细胞(AD-MSCs)进行了一项使用罗沙司他的研究,罗沙司他是一种特异性低氧模拟介质和 HIF-1α 诱导因子。评估了未经处理的 AD-间充质干细胞(第 1 组)、经罗沙司他预处理的 AD-间充质干细胞(第 2 组)、经 CAY10585 处理的 AD-间充质干细胞(第 3 组)、经 CAY10585 的罗沙司他预处理的 AD-间充质干细胞(第 4 组)和未经处理的原代腱细胞(第 5 组)的细胞形态、增殖率、致韧蛋白和基因表达水平。用 12.5µM 罗沙司他预处理 24 小时的间充质干细胞显示出最高的 HIF-1α 表达量,且不影响 AD-MSCs 的增殖率。然而,用 3.5µM CAY10585 处理细胞时,观察到 HIF-1α 水平明显降低。罗沙司他能明显上调胶原蛋白 I 和 III 的表达,上调幅度分别为 6.6 倍和 6.3 倍。HIF-1α 可促进硬骨、Tenascin-C 和胶原 III 的表达,分别增加了 6、7 和 3 倍。相反,使用 CAY10585 则会将这些表达量分别减少到 3、2 和 1 倍。这些趋势在第 1 组至第 4 组的基因表达水平中均可观察到,但与第 5 组相比,第 2 组中这些基因的表达量明显较低。 结论:HIF-1α 积累优于第 5 组:HIF-1α的积累促进了AD-间充质干细胞的细胞增殖和成腱分化,这表明罗沙司他可能是肌腱修复策略中的一种潜在治疗介质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hypoxia-induced HIF-1α accumulation promotes superior tenogenic differentiation potential of human adipose-derived mesenchymal stromal cells.

Tendon injuries remains a challenge to treat owing to its poor intrinsic reparative ability. It is hypothesised that hypoxic conditioning of mesenchymal stem cells (MSC) through the activation of hypoxia-inducible factor-1 alpha (HIF-1α), may enhance tendon repair process by promoting cellular proliferation and tenogenic differentiation. To demonstrate this, a study using roxadustat, a specific hypoxia mimetic mediator and HIF-1α inducer was conducted on adipose-derived mesenchymal stromal cells (AD-MSCs). Cellular morphology, proliferation rates, tenogenic protein and gene expression levels in untreated AD-MSCs (Group 1), roxadustat pre-conditioned AD-MSCs (Group 2), AD-MSCs subjected to CAY10585 (Group 3), roxadustat pre-conditioned AD-MSCs with CAY10585 (Group 4) and untreated primary tenocytes (Group 5) were evaluated. MSCs pre-conditioned with 12.5µM roxadustat for 24 hours showed the highest expression of HIF-1α without affecting the proliferation rates of AD-MSCs. However, significant reduction of HIF-1α levels was observed when the cells were treated with 3.5µM CAY10585. Roxadustat significantly up-regulated collagen I and III expressions by 6.6 and 6.3-fold respectively. HIF-1α promoted Scleraxis, Tenascin-C and Collagen III expressions, resulting in an increase of 6, 7, and 3 folds respectively. Conversely, using CAY10585 reduced these expressions to 3, 2 and 1 folds respectively. These trends were observed in the gene expression levels across Groups 1 to 4. However, the expression of these genes in Group 2 was significantly lower as compared to Group 5. Conclusion: HIF-1α accumulation promotes superior cell proliferation and tenogenic differentiation of AD-MSCs, indicating that roxadustat may be a potential therapeutic mediator in tendon repair strategies.

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来源期刊
Biotechnic & Histochemistry
Biotechnic & Histochemistry 生物-生物工程与应用微生物
CiteScore
3.40
自引率
6.20%
发文量
46
审稿时长
6-12 weeks
期刊介绍: Biotechnic & Histochemistry (formerly Stain technology) is the official publication of the Biological Stain Commission. The journal has been in continuous publication since 1926. Biotechnic & Histochemistry is an interdisciplinary journal that embraces all aspects of techniques for visualizing biological processes and entities in cells, tissues and organisms; papers that describe experimental work that employs such investigative methods are appropriate for publication as well. Papers concerning topics as diverse as applications of histochemistry, immunohistochemistry, in situ hybridization, cytochemical probes, autoradiography, light and electron microscopy, tissue culture, in vivo and in vitro studies, image analysis, cytogenetics, automation or computerization of investigative procedures and other investigative approaches are appropriate for publication regardless of their length. Letters to the Editor and review articles concerning topics of special and current interest also are welcome.
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