SP7基因沉默会抑制骨髓基质细胞肥大,但同时也会抑制软骨生成。

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING
Journal of Tissue Engineering Pub Date : 2023-06-21 eCollection Date: 2023-01-01 DOI:10.1177/20417314231177136
Rose Ann G Franco, Eamonn McKenna, Pamela G Robey, Ross W Crawford, Michael R Doran, Kathryn Futrega
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引用次数: 0

摘要

骨髓基质细胞(BMSC)要想在软骨修复中发挥作用,就必须克服其肥大分化倾向。一天的 TGF-β1 刺激可激活骨髓基质细胞的内在信号级联,进而驱动软骨和肥大分化。TGF-β1刺激可使SP7上调,SP7是一种已知有助于肥大分化的转录因子,即使随后从软骨诱导培养基中移除TGF-β1,SP7仍会保持上调。在这里,我们稳定地转导 BMSCs,使其表达旨在沉默 SP7 的 shRNA,并评估沉默 SP7 对肥大的缓解能力。SP7沉默抑制了肥大和软骨分化过程,导致微组织尺寸减小、糖胺聚糖生成受损以及软骨和肥大基因表达减少。因此,虽然SP7沉默抑制了肥大特征,但软骨源分化也受到了影响。我们进一步研究了SP7在单层成骨和成脂培养中的作用,发现沉默SP7分别抑制了特征性矿化和脂质空泡的形成。总的来说,SP7沉默会影响BMSCs的三系分化,但不足以将BMSC肥大与软骨形成分离开来。这些数据突显了在软骨组织工程策略中促进 BMSC 软骨形成的同时减少肥大所面临的挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

<i>SP7</i> gene silencing dampens bone marrow stromal cell hypertrophy, but it also dampens chondrogenesis.

<i>SP7</i> gene silencing dampens bone marrow stromal cell hypertrophy, but it also dampens chondrogenesis.

<i>SP7</i> gene silencing dampens bone marrow stromal cell hypertrophy, but it also dampens chondrogenesis.

SP7 gene silencing dampens bone marrow stromal cell hypertrophy, but it also dampens chondrogenesis.

For bone marrow stromal cells (BMSC) to be useful in cartilage repair their propensity for hypertrophic differentiation must be overcome. A single day of TGF-β1 stimulation activates intrinsic signaling cascades in BMSCs which subsequently drives both chondrogenic and hypertrophic differentiation. TGF-β1 stimulation upregulates SP7, a transcription factor known to contribute to hypertrophic differentiation, and SP7 remains upregulated even if TGF-β1 is subsequently withdrawn from the chondrogenic induction medium. Herein, we stably transduced BMSCs to express an shRNA designed to silence SP7, and assess the capacity of SP7 silencing to mitigate hypertrophy. SP7 silencing dampened both hypertrophic and chondrogenic differentiation processes, resulting in diminished microtissue size, impaired glycosaminoglycan production and reduced chondrogenic and hypertrophic gene expression. Thus, while hypertrophic features were dampened by SP7 silencing, chondrogenic differentation was also compromised. We further investigated the role of SP7 in monolayer osteogenic and adipogenic cultures, finding that SP7 silencing dampened characteristic mineralization and lipid vacuole formation, respectively. Overall, SP7 silencing affects the trilineage differentiation of BMSCs, but is insufficient to decouple BMSC hypertrophy from chondrogenesis. These data highlight the challenge of promoting BMSC chondrogenesis whilst simultaneously reducing hypertrophy in cartilage tissue engineering strategies.

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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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